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Publisher: Springer-Verlag   (Total: 2353 journals)

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Showing 1 - 200 of 2353 Journals sorted alphabetically
3D Research     Hybrid Journal   (Followers: 19, SJR: 0.214, h-index: 10)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 9, SJR: 1.073, h-index: 25)
AAPS J.     Hybrid Journal   (Followers: 20, SJR: 1.192, h-index: 74)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6, SJR: 0.718, h-index: 54)
Abdominal Imaging     Hybrid Journal   (Followers: 14, SJR: 0.723, h-index: 60)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 2, SJR: 0.447, h-index: 12)
Academic Psychiatry     Full-text available via subscription   (Followers: 22, SJR: 0.492, h-index: 32)
Academic Questions     Hybrid Journal   (Followers: 7, SJR: 0.135, h-index: 6)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26, SJR: 0.378, h-index: 30)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.355, h-index: 20)
Acoustics Australia     Hybrid Journal  
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.387, h-index: 6)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.624, h-index: 34)
Acta Biotheoretica     Hybrid Journal   (Followers: 5, SJR: 0.419, h-index: 25)
Acta Diabetologica     Hybrid Journal   (Followers: 14, SJR: 1.318, h-index: 46)
Acta Endoscopica     Hybrid Journal   (Followers: 1, SJR: 0.113, h-index: 8)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.465, h-index: 23)
Acta Geochimica     Hybrid Journal   (Followers: 4)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 1, SJR: 0.294, h-index: 13)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.818, h-index: 22)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.524, h-index: 32)
Acta Mathematica     Hybrid Journal   (Followers: 11, SJR: 8.021, h-index: 47)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.53, h-index: 29)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 5, SJR: 0.406, h-index: 30)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.451, h-index: 5)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.22, h-index: 20)
Acta Mechanica     Hybrid Journal   (Followers: 19, SJR: 0.898, h-index: 52)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.426, h-index: 29)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5, SJR: 0.525, h-index: 18)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.524, h-index: 14)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.833, h-index: 73)
Acta Neurologica Belgica     Hybrid Journal   (SJR: 0.348, h-index: 27)
Acta Neuropathologica     Hybrid Journal   (Followers: 5, SJR: 6.61, h-index: 117)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 17)
Acta Parasitologica     Hybrid Journal   (Followers: 9, SJR: 0.581, h-index: 28)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.551, h-index: 39)
Acta Politica     Hybrid Journal   (Followers: 13, SJR: 0.658, h-index: 20)
Activitas Nervosa Superior     Hybrid Journal  
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5, SJR: 0.103, h-index: 4)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 20, SJR: 0.871, h-index: 15)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 7)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 15, SJR: 0.795, h-index: 40)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.774, h-index: 52)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 3, SJR: 0.319, h-index: 15)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 34, SJR: 0.959, h-index: 44)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 15, SJR: 1.255, h-index: 44)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 54, SJR: 1.113, h-index: 14)
Advances in Gerontology     Partially Free   (Followers: 9, SJR: 0.141, h-index: 3)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 22, SJR: 1.397, h-index: 42)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.2, h-index: 4)
Advances in Polymer Science     Hybrid Journal   (Followers: 41, SJR: 0.637, h-index: 89)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 0.79, h-index: 44)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 7)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.882, h-index: 23)
Aerobiologia     Hybrid Journal   (Followers: 1, SJR: 0.511, h-index: 36)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.821, h-index: 49)
African Archaeological Review     Hybrid Journal   (Followers: 15, SJR: 0.612, h-index: 24)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.248, h-index: 6)
AGE     Hybrid Journal   (Followers: 7, SJR: 1.358, h-index: 33)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.337, h-index: 10)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.529, h-index: 55)
Agricultural Research     Hybrid Journal   (Followers: 3)
Agriculture and Human Values     Hybrid Journal   (Followers: 12, SJR: 1.197, h-index: 49)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.64, h-index: 56)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 10, SJR: 1.732, h-index: 59)
AI & Society     Hybrid Journal   (Followers: 7, SJR: 0.171, h-index: 19)
AIDS and Behavior     Hybrid Journal   (Followers: 13, SJR: 2.006, h-index: 71)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 3, SJR: 0.706, h-index: 19)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 3, SJR: 0.566, h-index: 18)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.388, h-index: 22)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 0.868, h-index: 20)
Algorithmica     Hybrid Journal   (Followers: 7, SJR: 0.898, h-index: 56)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.183, h-index: 20)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 4, SJR: 0.729, h-index: 20)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3, SJR: 1.392, h-index: 32)
AMBIO     Hybrid Journal   (Followers: 15, SJR: 1.094, h-index: 87)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 13, SJR: 0.864, h-index: 39)
American J. of Community Psychology     Hybrid Journal   (Followers: 23, SJR: 1.237, h-index: 83)
American J. of Criminal Justice     Hybrid Journal   (Followers: 6, SJR: 0.634, h-index: 13)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 11, SJR: 0.283, h-index: 3)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.175, h-index: 13)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.558, h-index: 35)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.293, h-index: 13)
American Sociologist     Hybrid Journal   (Followers: 12, SJR: 0.18, h-index: 13)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.362, h-index: 83)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 5, SJR: 0.21, h-index: 37)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 3, SJR: 0.665, h-index: 7)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 28, SJR: 1.096, h-index: 123)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.301, h-index: 26)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.212, h-index: 69)
Animal Cognition     Hybrid Journal   (Followers: 16, SJR: 1.122, h-index: 55)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.156, h-index: 4)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.377, h-index: 32)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.504, h-index: 14)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.167, h-index: 26)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 11, SJR: 2.112, h-index: 98)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.182, h-index: 94)
Annals of Combinatorics     Hybrid Journal   (Followers: 3, SJR: 0.849, h-index: 15)
Annals of Data Science     Hybrid Journal   (Followers: 9)
Annals of Dyslexia     Hybrid Journal   (Followers: 9, SJR: 0.857, h-index: 40)
Annals of Finance     Hybrid Journal   (Followers: 28, SJR: 0.686, h-index: 14)
Annals of Forest Science     Hybrid Journal   (Followers: 4, SJR: 0.929, h-index: 57)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.136, h-index: 23)
Annals of Hematology     Hybrid Journal   (Followers: 14, SJR: 1.117, h-index: 62)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 6, SJR: 0.593, h-index: 42)
Annals of Microbiology     Hybrid Journal   (Followers: 10, SJR: 0.402, h-index: 26)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 5, SJR: 0.68, h-index: 45)
Annals of Operations Research     Hybrid Journal   (Followers: 8, SJR: 1.186, h-index: 78)
Annals of Ophthalmology     Hybrid Journal   (Followers: 10)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.405, h-index: 42)
Annals of Software Engineering     Hybrid Journal   (Followers: 12)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 10, SJR: 0.553, h-index: 8)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 13, SJR: 1.902, h-index: 127)
Annals of Telecommunications     Hybrid Journal   (Followers: 7, SJR: 0.315, h-index: 25)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.931, h-index: 31)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.992, h-index: 87)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.14, h-index: 57)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.554, h-index: 87)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.354, h-index: 27)
Applications of Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.274, h-index: 20)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 44, SJR: 0.575, h-index: 80)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17, SJR: 0.267, h-index: 26)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.361, h-index: 21)
Applied Composite Materials     Hybrid Journal   (Followers: 48, SJR: 0.705, h-index: 35)
Applied Entomology and Zoology     Partially Free   (Followers: 2, SJR: 0.554, h-index: 34)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.323, h-index: 9)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.541, h-index: 13)
Applied Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.777, h-index: 43)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.358, h-index: 34)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 4, SJR: 0.955, h-index: 33)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.275, h-index: 8)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 4, SJR: 0.37, h-index: 26)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 62, SJR: 1.262, h-index: 161)
Applied Physics A     Hybrid Journal   (Followers: 7, SJR: 0.535, h-index: 121)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 23, SJR: 0.983, h-index: 104)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.677, h-index: 47)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 10, SJR: 0.288, h-index: 15)
Applied Solar Energy     Hybrid Journal   (Followers: 17, SJR: 0.251, h-index: 6)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 4, SJR: 0.351, h-index: 9)
Aquaculture Intl.     Hybrid Journal   (Followers: 22, SJR: 0.613, h-index: 40)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
Aquatic Ecology     Hybrid Journal   (Followers: 30, SJR: 0.646, h-index: 44)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.764, h-index: 39)
Aquatic Sciences     Hybrid Journal   (Followers: 12, SJR: 1.172, h-index: 53)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.345, h-index: 20)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 1, SJR: 0.417, h-index: 16)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 21, SJR: 1.056, h-index: 15)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.397, h-index: 13)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.597, h-index: 29)
Archival Science     Hybrid Journal   (Followers: 53, SJR: 0.804, h-index: 22)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.28, h-index: 15)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 1, SJR: 0.946, h-index: 23)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 4.091, h-index: 66)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 4, SJR: 0.865, h-index: 40)
Archives and Museum Informatics     Hybrid Journal   (Followers: 122)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 4, SJR: 2.841, h-index: 40)
Archives of Dermatological Research     Hybrid Journal   (Followers: 6, SJR: 0.9, h-index: 65)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.846, h-index: 84)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 17, SJR: 0.695, h-index: 47)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.702, h-index: 85)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.039, h-index: 56)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 1.092, h-index: 13)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 9, SJR: 1.198, h-index: 74)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.595, h-index: 76)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 1.086, h-index: 90)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 13, SJR: 1.264, h-index: 50)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 1.2, h-index: 42)
ArgoSpine News & J.     Hybrid Journal   (SJR: 0.102, h-index: 3)
Argumentation     Hybrid Journal   (Followers: 5, SJR: 0.295, h-index: 18)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.948, h-index: 22)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 1, SJR: 0.797, h-index: 17)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.145, h-index: 8)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 10, SJR: 0.288, h-index: 25)
Artificial Intelligence Review     Hybrid Journal   (Followers: 14, SJR: 0.948, h-index: 48)
Artificial Life and Robotics     Hybrid Journal   (Followers: 8, SJR: 0.231, h-index: 14)
Asia Europe J.     Hybrid Journal   (Followers: 4, SJR: 0.247, h-index: 9)
Asia Pacific Education Review     Hybrid Journal   (Followers: 9, SJR: 0.371, h-index: 17)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 12, SJR: 1.676, h-index: 50)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 11, SJR: 0.353, h-index: 13)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.19, h-index: 15)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 20, SJR: 1.006, h-index: 14)
Asian Business & Management     Hybrid Journal   (Followers: 7, SJR: 0.41, h-index: 10)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 7)
Asian J. of Criminology     Hybrid Journal   (Followers: 5, SJR: 0.263, h-index: 8)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.681, h-index: 15)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.195, h-index: 5)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover Archivum Immunologiae et Therapiae Experimentalis
  [SJR: 1.2]   [H-I: 42]   [2 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1661-4917 - ISSN (Online) 0004-069X
   Published by Springer-Verlag Homepage  [2353 journals]
  • Apportioning Blame: Autoreactive CD4 + and CD8 + T Cells in Type 1
           Diabetes
    • Authors: Rubén Varela-Calvino; Cristina Calviño-Sampedro; Iria Gómez-Touriño; Oscar J. Cordero
      Pages: 275 - 284
      Abstract: Abstract Type 1 diabetes (T1D) is one of the most studied archetypal organ-specific autoimmune diseases. Although many clinical, epidemiological, and pathological characteristics have been described, there are still important issues which need to be resolved as these will have a major impact on the development of future antigen-specific immunotherapies. An important question relates to T lymphocytes in the development of the disease, in particular their role in the destruction of insulin-producing beta cells. Since the discovery that certain class II histocompatibility complex molecules (HLA) are linked to the development of T1D, much research has focused on CD4+ helper T lymphocytes; however, recent studies highlight class I HLA molecules as an independent risk factor; hence, research into the role played by CD8+ cytotoxic T lymphocytes has gained momentum. In this review, we summarize recent studies clarifying the role played by both sets of autoreactive T lymphocytes in T1D, discuss the targets recognized by these cells and their phenotype in T1D patients. Finally, we will examine the possible generation of regulatory CD8+ T lymphocytes upon different immuno-intervention strategies.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-016-0452-4
      Issue No: Vol. 65, No. 4 (2017)
       
  • Perillyl alcohol, a pleiotropic natural compound suitable for brain tumor
           therapy, targets free radicals
    • Authors: Aline C. Gomes; Angélica L. Mello; Manuel G. Ribeiro; Diogo G. Garcia; Clovis O. Da Fonseca; Marcela D’Alincourt Salazar; Axel H. Schönthal; Thereza Quirico-Santos
      Pages: 285 - 297
      Abstract: Abstract Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis. When cells are subjected to oxidative stress conditions, there is an accumulation of ROS that can lead to irreversible cell injury caused primarily by lipid peroxidation, protein aggregation and/or DNA damage. Malignant tumors, such as glioblastoma multiforme, display elevated rates of oxygen consumption, necrosis and abnormal structural microvasculature. Alterations in the tumor microenvironment are tightly linked to tumor progression and occur as a result of activation of complex signaling networks involving inter-clonal cooperation, cell–matrix interactions and an ongoing inflammatory response leading to genetic and epigenetic alterations. This review will focus on the pro- and anti-oxidant activities of POH, which are greatly dependent on the respective ROS levels within the tumor microenvironment and involve the ER stress response system. As well, some critical aspects of tumor-associated metabolic changes and the consequences of endogenous ROS production for tumor progression will be discussed.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-017-0459-5
      Issue No: Vol. 65, No. 4 (2017)
       
  • Primary Biliary Cholangitis Associated with Skin Disorders: A Case Report
           and Review of the Literature
    • Authors: Benedetta Terziroli Beretta-Piccoli; Caroline Guillod; Igor Marsteller; Roland Blum; Luca Mazzucchelli; Chiara Mondino; Pietro Invernizzi; M. Eric Gershwin; Carlo Mainetti
      Pages: 299 - 309
      Abstract: Abstract Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune diseases. Skin disorders are sporadically reported in association with PBC. We report an unusual case of PBC associated with acquired reactive perforating dermatosis (ARPD) and present a review of the literature on skin disorders associated with PBC. Our patient presented to the dermatology department with generalized pruritus associated with nodular perforating skin lesions on the trunk, and cholestatic liver disease of unknown origin. After having established both diagnosis of ARPD and PBC, she was managed in an interdisciplinary manner, and both her skin and liver conditions improved gradually. Only one similar case is reported in the literature, in that case, the liver disease was not treated. By reviewing the literature, we found that lichen planus, vitiligo, and psoriasis are the most frequent skin disorders associated with PBC. However, there is only limited data about specific skin disorders associated with PBC. This case report of a patient with PBC associated with ARPD underlines the importance of interdisciplinary management of patients with rare liver diseases combined with rare skin disorders. The present review of the literature shows that probably, immune-mediated skin conditions are not more frequent in PBC patients than in the general population. However, the available data are scant; there is a need for high-quality data on skin conditions associated with PBC.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-016-0448-0
      Issue No: Vol. 65, No. 4 (2017)
       
  • Functions of Cancer-Derived Extracellular Vesicles in Immunosuppression
    • Authors: Liliana Czernek; Markus Düchler
      Pages: 311 - 323
      Abstract: Abstract Extracellular vesicles, including exosomes, constitute an important element of intercellular communication by carrying a variety of molecules from producer to target cells. The transport of mRNA and miRNA can directly modulate gene expression in the target cells. The miRNA content in exosomes is characteristic for the cell from which the vesicles were derived enabling the usage of exosomes as biomarkers for the diagnosis various diseases, including cancer. Cancer-derived exosomes support the survival and progression of tumors in many ways and also contribute to the neutralization of the anti-cancer immune response. Exosomes participate in all known mechanisms by which cancer evades the immune system. They influence the differentiation and activation of immune suppressor cells, they modulate antigen presentation, and are able to induce T-cell apoptosis. Although cancer-derived exosomes mainly suppress the immune system and facilitate tumor progression, they are also important sources of tumor antigens with potential clinical application in stimulating immune responses. This review summarizes how exosomes assist cancer to escape immune recognition and to acquire control over the immune system.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-016-0453-3
      Issue No: Vol. 65, No. 4 (2017)
       
  • Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines,
           inducible NOS (NOS type II), and myelin proteins in animal model of
           multiple sclerosis
    • Authors: Natalia Lubina-Dąbrowska; Adam Stepień; Grzegorz Sulkowski; Beata Dąbrowska-Bouta; Józef Langfort; Małgorzata Chalimoniuk
      Pages: 325 - 338
      Abstract: Abstract The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund’s complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-β1a or IFN-β1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-β1b and IFN-β1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-β1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-β1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-017-0458-6
      Issue No: Vol. 65, No. 4 (2017)
       
  • Pre-Pregnancy Levels of Peripheral Natural Killer Cells as Markers for
           Immunomodulatory Treatment in Patients with Recurrent Miscarriage
    • Authors: Ruben J. Kuon; Franziska Müller; Kilian Vomstein; Maja Weber; Hannes Hudalla; Sabine Rösner; Thomas Strowitzki; Udo Markert; Volker Daniel; Bettina Toth
      Pages: 339 - 346
      Abstract: Abstract Immunological risk factors in patients with recurrent miscarriage (RM) are discussed controversially. Abnormalities of natural killer cells (NK) have been described in RM patients. Lipid infusions are known to modulate lymphocyte subsets. The aim of this study was to identify immune parameters that predict success of treatment with lipid infusions in RM patients with elevated NK. In sum, n = 341 couples with RM were screened for established risk factors and peripheral lymphocyte subpopulations as well as uterine NK cells. We identified n = 136 patients with ≥ 2 consecutive RM and elevated NK. So far, n = 40 RM patients with NK disorders were treated with lipid infusions starting at positive pregnancy test, every 2 weeks until 12 + 0 weeks of gestation (GW) or miscarriage. The pre-pregnancy immune diagnostics in idiopathic RM (iRM) patients with ongoing pregnancy were compared to the group with miscarriages and healthy controls (n = 15). Pre-pregnancy immune diagnostics differed significantly between the groups, with significant higher levels of peripheral NK (% and /µL) in iRM patients who miscarried again compared to controls (p = 0.0035 and p = 0.0019). Furthermore, iRM patients show lower percentages of CD3+ lymphocytes than healthy controls (p = 0.0049). In n = 22/40 (55%) patients, pregnancy is ongoing >12 + 0 GW. RM patients with very high pre-pregnancy peripheral NK (pNK) lymphocytes might not benefit from lipid infusions. Pre-pregnancy immunomodulatory treatment in RM patients might be helpful to lower pNK levels and establish an immune environment which is supportive for fetal development.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-017-0457-7
      Issue No: Vol. 65, No. 4 (2017)
       
  • Sildenafil, a Phosphodiesterase Type 5 Inhibitor, Downregulates
           Osteopontin in Human Peripheral Blood Mononuclear Cells
    • Authors: Beata Kaleta; Agnieszka Boguska
      Pages: 347 - 353
      Abstract: Abstract The aim of this study was to investigate the ability of sildenafil to regulate osteopontin (OPN) gene and protein in peripheral blood mononuclear cells (PBMCs) from healthy blood donors. OPN is expressed by a wide variety of cell types, including immune cells. OPN functions are linked to various physiological and pathological conditions. Sildenafil is a selective inhibitor of type 5 phosphodiesterase. Sildenafil has recently been found to have immunomodulatory effects in animal models and in studies performed in humans. PMA-stimulated and unstimulated PBMCs from 16 healthy blood donors (men) were cultured with sildenafil (at concentrations of 400 ng/ml and 4 µg/ml). OPN level in culture supernatants was measured by enzyme-linked immunosorbent assay. The analysis of OPN gene expression was performed by real-time PCR. Cell viability was assessed by trypan blue staining. PMA plus ionomycin stimulation of PBMCs resulted in a significant increase of OPN production and gene expression (p < 0.001). Sildenafil significantly decreased OPN secretion (p < 0.05) and gene expression (p < 0.05) in stimulated PBMCs; however, had no effect on OPN in unstimulated PBMCs. Sildenafil did not affect PBMCs viability. Sildenafil downregulates OPN in PBMCs from healthy men. Despite accumulating evidence for the immunomodulatory effects of sildenafil on human immune system cells, further studies are needed to determine if this drug affects the level of cGMP and NF-κB in PBMCs. In addition, it is needed to evaluate sildenafil’s activity in PBMCs from patients with elevated OPN levels.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-017-0455-9
      Issue No: Vol. 65, No. 4 (2017)
       
  • The Effect of Nonsurgical Periodontal Therapy on HNP1-3 Level in Gingival
           Crevicular Fluid of Chronic Periodontitis Patients
    • Authors: Ewa Dolińska; Anna Skurska; Małgorzata Pietruska; Violetta Dymicka-Piekarska; Robert Milewski; Jan Pietruski; Anton Sculean
      Pages: 355 - 361
      Abstract: Abstract The rich bacterial flora of oral cavity is controlled by innate immune response, including antibacterial peptides and among them human neutrophil peptides 1–3 (HNP1-3). The knowledge of the involvement of HNPs in innate and acquired immunity of the periodontium is fragmentary. The aim of the study was to assess alterations in HNP1-3 levels in the gingival crevicular fluid (GCF) of chronic periodontitis patients before and after nonsurgical periodontal therapy. Nineteen patients with chronic periodontitis were qualified to the study. After periodontal examination, one site with pocket depth (PD) ≥4 mm was selected. All the patients received periodontal treatment involving scaling and root planing with additional systemic antibiotic therapy (Amoxicillin 375 mg three times daily and Metronidazole 250 mg three times daily for 7 days). Prior to therapy, 3 and 6 months after it, clinical periodontal parameters were measured and GCF was collected from previously chosen site. The level of HNP1-3 in GCF was determined by means of a commercially available enzyme-linked immunoassay kit. The periodontal therapy caused a statistically significant (p < 0.001) decrease in all the assessed clinical parameters at the sites of sample collection except for bleeding on probing. The level of HNP1-3 per measure point showed a statistically significant increase (baseline—3 months: p = 0.05, baseline—6 months: p = 0.007). Within the limits of the study, it can be stated that nonsurgical periodontal therapy with additional systemic administration of Amoxicillin and Metronidazole increases the level of HNP1-3 in GCF.
      PubDate: 2017-08-01
      DOI: 10.1007/s00005-016-0451-5
      Issue No: Vol. 65, No. 4 (2017)
       
  • The Impact of Sex and Age on the Prevalence of Clinically Relevant
           Sensitization and Asymptomatic Sensitization in the General Population
    • Authors: Anna Dor-Wojnarowska; Jerzy Liebhart; Jadwiga Miecielica; Marek Rabski; Andrzej Fal; Bolesław Samoliński; Marita Nittner-Marszalska
      Pages: 253 - 261
      Abstract: Abstract The objective of our study was to evaluate the impact of sex and age on the prevalence of sensitization to inhalant allergens. The study was performed as a part of Polish Epidemiology of Allergic Diseases study, and data concerning citizens of Wroclaw were analyzed. The participants were divided into three age groups (6–7, 13–14, and 20–44 years) with a subdivision according to sex. We randomly selected 1409 individuals, 439 people complied; the complete set of tests was performed on 421 of them. We found that 37.7 % of the study population demonstrated sensitization to at least one of the allergens tested. Positive skin tests were found more frequently in males than in females (p = 0.003); among 6–7-year-old children, the sensitization was independent of sex (p = 0.26), while in two other groups, it was higher in males (p = 0.002 and p = 0.03, respectively). Clinically asymptomatic sensitization (AS) was found more often in females than in males (p = 0.04). The higher rate of AS in women was observed only in the two younger age groups, while in the 20–44-year-old group AS did not differ between the sexes (p = 0.72). Female sex hormones may contribute to a later change in the nature of sensitization from clinically asymptomatic to symptomatic. Further studies are needed to confirm the results of our study.
      PubDate: 2017-06-01
      DOI: 10.1007/s00005-016-0425-7
      Issue No: Vol. 65, No. 3 (2017)
       
  • Activated and Memory T Lymphocytes in Children with Gaucher Disease
    • Authors: Asmaa M. Zahran; Azza A. Eltayeb; Khalid I. Elsayh; Khaled Saad; Faisal-Alkhateeb Ahmad; Ahmad I. M. Ibrahim
      Pages: 263 - 269
      Abstract: Abstract Gaucher disease (GD) is the most prevalent lysosomal storage disorder. Gaucher disease is associated with remarkable alterations in the immune system, and GD patients are more susceptible to infections and are at a higher risk of developing autoimmune disorders and malignancies. In a case–control study, we used three-color flow cytometric immunophenotyping for determination of the frequency of lymphocyte subpopulations and activated T lymphocytes among 18 children with GD1 under enzyme replacement therapy managed in Assiut University Hospitals. We found significant increases in the frequencies of total lymphocytes, CD19+, CD3+, CD4+, and CD8+ in children with GD1 when compared to healthy control. The frequencies of activated T lymphocytes (CD3+HLA-DR+), activated T-helper cells (CD4+HLA-DR+), and activated T-suppressor/cytotoxic cells (CD8+HLA-DR+) were significantly higher in GD1 as compared to healthy children. Our data show that the increased proportion of activated T lymphocytes in children with GD1 raises the issue of their possible involvement in the pathogenesis of the immune dysfunction seen in these patients. Our data suggested that the activated T lymphocytes could play a role in the clinical course of GD1. The relationship of these cells to immune disorders in GD1 children remains to be determined.
      PubDate: 2017-06-01
      DOI: 10.1007/s00005-016-0421-y
      Issue No: Vol. 65, No. 3 (2017)
       
  • Comparative Assessment of Induced Immune Responses Following Intramuscular
           Immunization with Fusion and Cocktail of LeIF, LACK and TSA Genes Against
           Cutaneous Leishmaniasis in BALB/c Mice
    • Authors: Nahid Maspi; Fatemeh Ghaffarifar; Zohreh Sharifi; Abdolhossein Dalimi; Mohammad Saaid Dayer
      Abstract: Abstract In the present study, we evaluated induced immune responses following DNA vaccine containing cocktail or fusion of LeIF, LACK and TSA genes or each gene alone. Mice were injected with 100 µg of each plasmid containing the gene of insert, plasmid DNA alone as the first control group or phosphate buffer saline as the second control group. Then, cellular and humoral responses, lesion size were measured for all groups. All vaccinated mice induced Th1 immune responses against Leishmania characterized by higher IFN-γ and IgG2a levels compared with control groups (p < 0.05). In addition, IFN-γ levels increased in groups immunized with fusion and cocktail vaccines in comparison with LACK (p < 0.001) and LeIF (p < 0.01) groups after challenge. In addition, fusion and cocktail groups produced higher IgG2a values than groups vaccinated with a gene alone (p < 0.05). Lesion progression delayed for all immunized groups compared with control groups from 5th week post-infection (p < 0.05). Mean lesion size decreased in immunized mice with fusion DNA than three groups vaccinated with one gene alone (p < 0.05). While, lesion size decreased significantly in cocktail recipient group than LeIF recipient group (p < 0.05). There was no difference in lesion size between fusion and cocktail groups. Overall, immunized mice with cocktail and fusion vaccines showed stronger Th1 response by production of higher IFN-γ and IgG2a and showed smaller mean lesion size. Therefore, use of multiple antigens can improve induced immune responses by DNA vaccination.
      PubDate: 2017-08-04
      DOI: 10.1007/s00005-017-0484-4
       
  • The PD-1/PD-L1 Inhibitory Pathway is Altered in Primary
           Glomerulonephritides
    • Authors: Ewelina Grywalska; Iwona Smarz-Widelska; Ewelina Krasowska-Zajac; Izabela Korona-Glowniak; Karolina Zaluska-Patel; Michal Mielnik; Martyna Podgajna; Anna Malm; Jacek Rolinski; Wojciech Zaluska
      Abstract: Abstract The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time. The study included peripheral blood (PB) samples from 20 newly diagnosed PGN and NPGN patients. The control group comprised of 20 healthy age- and sex-matched subjects. The viable PB lymphocytes underwent labelling with fluorochrome-conjugated monoclonal antibodies anti-PD-1 and anti-PD-L1, and were analyzed using a flow cytometer. The frequencies of CD4+/PD1+ T lymphocytes, CD8+/PD1+ T lymphocytes, and CD19+/PD-1+ B lymphocytes in the PGN group exceeded values obtained both in the NPGN group, and the control group. Alteration of PD-1/PD-L1 pathway may be involved in poorer prognosis, as patients with PGN are characterized by higher frequencies of PD-1-positive and PD-L1-positive T and B lymphocytes than patients with NPGN. Our results suggest that deregulation of PD-1/PD-L1 axis may contribute to the PGN and NPGN pathogenesis. High percentages of lymphocytes with PD-1 and PD-L1 expression may be related to the continuous T-cell activation and development of glomerular inflammation and injury.
      PubDate: 2017-08-02
      DOI: 10.1007/s00005-017-0485-3
       
  • STING Signaling in Cancer Cells: Important or Not'
    • Authors: Olga Sokolowska; Dominika Nowis
      Abstract: Abstract Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response. Therefore, STING agonists are now being extensively developed as a new class of cancer therapeutics. However, little is known about the consequences of activated STING-mediated signaling in cancer cells on the efficacy of the antitumor treatment. It has been shown that activation of the STING-dependent pathway in cancer cells can result in tumor infiltration with immune cells and modulation of the anticancer immune response. Understanding the function of STING pathway in cancer cells might provide important insights into the development of effective therapeutic strategies. This review focuses on the role of STING pathway in cancer cells, the largely unknown topic that has recently emerged to be important in the context of STING-mediated antitumor responses.
      PubDate: 2017-07-26
      DOI: 10.1007/s00005-017-0481-7
       
  • Role of TGF-β in Self-Peptide Regulation of Autoimmunity
    • Authors: Bhagirath Singh; Michael D. Krawetz; Rachel M. De Lima; Rinee Mukherjee; Pratibha Chaturvedi; Edwin Lee-Chan; Edward H. Leiter; Kelly L. Summers
      Abstract: Abstract Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins. B:9-23) that protected NOD mice from T1D. Immunization of NOD mice with the self-MHC class II I-Ag7 β-chain-derived peptide, I-Aβg7 p54-76 also induced large amounts of TGF-β and also protected these mice from diabetes development. These results indicate that peptides derived from disease related self-antigens and MHC class II molecules primarily induce TGF-β producing regulatory Th3 and Tr1-like cells. TGF-β produced by these cells could enhance the differentiation of induced regulatory iTreg and iTreg17 cells to prevent induction and progression of autoimmune diseases. We therefore suggest that peripheral immune tolerance could be induced and maintained by immunization with self-peptides that induce TGF-β producing T cells.
      PubDate: 2017-07-21
      DOI: 10.1007/s00005-017-0482-6
       
  • Possible Immunomodulating Effect of Retinol on Cytokines Secretion in
           Patients with Recurrent Furunculosis
    • Authors: Danuta Nowicka; Ewelina Grywalska; Anna Hymos; Michał Mielnik; Jacek Roliński
      Abstract: Abstract Recurrent furunculosis is an infection of hair follicles which results in formation of abscesses. Previous studies showed that the pathogenesis of the disease may include an immune-mediated component as the proliferative response of peripheral blood lymphocytes to staphylococcal antigen is depressed. The aim of our study was to evaluate cytokines concentration in the plasma of patients with recurrent furunculosis and to determine whether retinol affects the secretion of those cytokines in patients with recurrent furunculosis and healthy subjects. Blood samples were taken from 15 patients with recurrent furunculosis and 15 age-matched healthy subjects. A quantitative determination of selected cytokines (IL-17, 13, 2, 10, 4, IFN-γ, TNF-α) was performed in the plasma at baseline and after 72-h culture of peripheral blood mononuclear cells with and without retinol in both groups. In the plasma of patients with recurrent furunculosis, concentration of IL-10, 2, and TNF-α was significantly higher, whereas IL-13 significantly lower when compared with healthy subjects. After retinol stimulation, the concentration of IL-17 and IFN-γ increased significantly in both groups. Secretion of anti-inflammatory cytokines, especially IL-10 (p < 0.002) and 13 (p < 0.01), achieved lower levels in recurrent furunculosis samples than in those of healthy controls. Network of cytokines differs in patients with recurrent furunculosis from healthy subjects. Retinol stimulation affects secretion of both pro-inflammatory and anti-inflammatory cytokines. Further studies are recommended for better understanding the pathomechanism of recurrent furunculosis and potential clinical use of retinol in patients affected by recurrent furunculosis.
      PubDate: 2017-07-20
      DOI: 10.1007/s00005-017-0483-5
       
  • Tumor-Associated Macrophages as Target for Antitumor Therapy
    • Authors: Katarzyna Sawa-Wejksza; Martyna Kandefer-Szerszeń
      Abstract: Abstract It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-β, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.
      PubDate: 2017-06-28
      DOI: 10.1007/s00005-017-0480-8
       
  • Anti-GITR Antibody Treatment Increases TCR Repertoire Diversity of
           Regulatory but not Effector T Cells Engaged in the Immune Response Against
           B16 Melanoma
    • Authors: Bozena Scirka; Edyta Szurek; Maciej Pietrzak; Grzegorz Rempala; Pawel Kisielow; Leszek Ignatowicz; Arkadiusz Miazek
      Abstract: Abstract Crosslinking of glucocorticoid-induced TNF family-related receptor (GITR) with agonist antibodies restores cancer immunity by enhancing effector T cell (Teff) responses while interfering with intra-tumor regulatory T cell (Treg) stability and/or accumulation. However, how anti-GITR antibody infusion changes T cell receptor (TCR) repertoire of Teffs and Tregs engaged in anti-tumor immune response is unclear. Here, we used a transgenic mouse model (TCRmini) where T cells express naturally generated but limited TCR repertoire to trace the fate of individual T cells recognizing B16 melanoma in tumor-bearing mice, treated or non-treated with an anti-GITR monoclonal antibody DTA-1. Analysis of TCRs of CD4+ T cells from these mice revealed that the TCR repertoire of dominant tumor-reactive Teff clones remained rather similar in treated and non-treated mice. In contrast, both tumor-associated and peripheral TCR repertoire of Tregs, which were mostly distinct from that of Teffs, underwent DTA-1 mediated remodeling characterized by depletion of dominant clones and an emergence of more diverse, low-frequency clones bearing increased numbers of TCRs shared with Teffs. We conclude that the DTA-1 infusion eliminates activated Tregs engaged in the initial maintenance of tolerogenic niche for tumor growth, but over time, it favors tumor replenishment by Tregs expressing an array of TCRs able to compete with Teffs for recognition of the same tumor antigens which may prevent its complete eradication.
      PubDate: 2017-06-21
      DOI: 10.1007/s00005-017-0479-1
       
  • Skin Immunity
    • Authors: Agata Matejuk
      Abstract: Abstract Skin is the largest organ of the body with a complex network of multitude of cell types that perform plastic and dynamic cellular communication to maintain several vital processes such as inflammation, immune response including induction of tolerance and disease prevention, wound healing, and angiogenesis. Of paramount importance are immunological functions of the skin that protect from harmful exposure coming from external and internal environments. Awareness of skin immunity can provide a better comprehension of inflammation, autoimmunity, cancer, graft-versus-host disease, vaccination, and immunotherapy approaches. This paper will update on what we currently know about immune sentinels contributing to skin immunity.
      PubDate: 2017-06-16
      DOI: 10.1007/s00005-017-0477-3
       
  • Exocrine Gland Morphogenesis: Insights into the Role of Amphiregulin from
           Development to Disease
    • Authors: Margherita Sisto; Loredana Lorusso; Giuseppe Ingravallo; Sabrina Lisi
      Abstract: Abstract Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjögren’s syndrome.
      PubDate: 2017-06-07
      DOI: 10.1007/s00005-017-0478-2
       
  • The Immune Response in Periodontal Tissues
    • Authors: Małgorzata Nędzi-Góra; Jan Kowalski; Renata Górska
      Abstract: Abstract The uniqueness of periodontal diseases is caused by several factors. This group of diseases is caused by numerous bacterial species formed in the dental biofilm, and one cannot distinguish the specific pathogen that is responsible for the disease initiation or progress (though Gram-negative anaerobic rods are associated with the advanced form of the disease). The disease is both infectious and inflammatory in its nature, and in the state of health there is always a subclinical level of inflammatory response, caused by the so-called harmless bacteria. Negligence in oral hygiene may result in maturation of the biofilm and trigger host response, manifesting clinically as gingivitis or—later and in susceptible subjects—as periodontitis. The article presents the contemporary knowledge of the inflammatory reaction occurring in tissues surrounding the tooth during periodontal inflammation. The most important mechanisms are described, together with implications for clinicists.
      PubDate: 2017-06-06
      DOI: 10.1007/s00005-017-0472-8
       
 
 
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