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Autoimmunity t cell

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https://www.readbyqxmd.com/read/28230210/synergistic-suppression-of-autoimmune-arthritis-through-concurrent-treatment-with-tolerogenic-dc-and-msc
#1
Rong Li, Yujuan Zhang, Xiufen Zheng, Shanshan Peng, Keng Yuan, Xusheng Zhang, Weiping Min
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#2
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#3
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228726/current-diagnosis-and-management-of-immune-related-adverse-events-iraes-induced-by-immune-checkpoint-inhibitor-therapy
#4
REVIEW
Vivek Kumar, Neha Chaudhary, Mohit Garg, Charalampos S Floudas, Parita Soni, Abhinav B Chandra
The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agents like tremelimumab and atezolimumab for use in patients with advanced stage mesothelioma and urothelial carcinoma respectively. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28228650/haematopoietic-stem-cell-transplantation-for-autoimmune-diseases
#5
REVIEW
Joost F Swart, Eveline M Delemarre, Femke van Wijk, Jaap-Jan Boelens, Jürgen Kuball, Jacob M van Laar, Nico M Wulffraat
Autologous haematopoietic stem cell transplantation (HSCT) is the only treatment that is able to induce long-term, drug-free and symptom-free remission in several refractory autoimmune rheumatic diseases. Over 3,000 HSCT procedures for rheumatic and nonrheumatic severe autoimmune diseases have been performed worldwide. Specific conditioning regimens are currently used to eradicate the autoreactive immunological memory of patients. Although in vivo immune cell depletion with antithymocyte globulin or anti-CD52 is the norm for many regimens, ex vivo selection of CD34(+) stem cells from the graft is controversial...
February 23, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28228602/a-divergent-population-of-autoantigen-responsive-cd4-t-cells-in-infants-prior-to-%C3%AE-cell-autoimmunity
#6
Anne-Kristin Heninger, Anne Eugster, Denise Kuehn, Florian Buettner, Matthias Kuhn, Annett Lindner, Sevina Dietz, Sibille Jergens, Carmen Wilhelm, Andreas Beyerlein, Anette-G Ziegler, Ezio Bonifacio
Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen-responsive CD4(+) T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen-responsive naïve CD4(+) T cells from children who developed β cell autoimmunity was found in infancy, well before the appearance of β cell antigen-specific memory T cells or autoantibodies...
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28228281/dysregulation-of-the-cytokine-gm-csf-induces-spontaneous-phagocyte-invasion-and-immunopathology-in-the-central-nervous-system
#7
Sabine Spath, Juliana Komuczki, Mario Hermann, Pawel Pelczar, Florian Mair, Bettina Schreiner, Burkhard Becher
Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral helper T (Th) cells. Antigen-independent GM-CSF release led to the invasion of inflammatory myeloid cells into the central nervous system (CNS), which was accompanied by the spontaneous development of severe neurological deficits...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228257/t-regulatory-cells-support-plasma-cell-populations-in-the-bone-marrow
#8
Arielle Glatman Zaretsky, Christoph Konradt, Fabien Dépis, James B Wing, Radhika Goenka, Daniela Gomez Atria, Jonathan S Silver, Sunglim Cho, Amaya I Wolf, William J Quinn, Julie B Engiles, Dorothy C Brown, Daniel Beiting, Jan Erikson, David Allman, Michael P Cancro, Shimon Sakaguchi, Li-Fan Lu, Christophe O Benoist, Christopher A Hunter
Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP(+) cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226225/thymic-epithelial-cells
#9
Jakub Abramson, Graham Anderson
IntrathymicTcell development is a complex process that depends upon continuous guidance from thymus stromal cell microenvironments. The thymic epithelium within the thymic stroma comprises highly specialized cells with a high degree of anatomic, phenotypic, and functional heterogeneity. These properties are collectively required to bias thymocyte development toward production of self-tolerant and functionally competent T cells. The importance of thymic epithelial cells (TECs) is evidenced by clear links between their dysfunction and multiple diseases where autoimmunity and immunodeficiency are major components...
February 10, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28224733/nk1-1-cd4-nkg2d-t-cells-suppress-dss-induced-colitis-in-mice-through-production-of-tgf-%C3%AE
#10
Xingxing Qian, Chunxia Hu, Sen Han, Zhijie Lin, Weiming Xiao, Yanbing Ding, Yu Zhang, Li Qian, Xiaoqing Jia, Guoqiang Zhu, Weijuan Gong
CD4(+) NKG2D(+) T cells are associated with tumour, infection and autoimmune diseases. Some CD4(+) NKG2D(+) T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4(+) NKG2D(+) T cells were further classified into NK1.1(-) CD4(+) NKG2D(+) and NK1.1(+) CD4(+) NKG2D(+) subpopulations. The frequency of NK1.1(-) CD4(+) NKG2D(+) cells decreased in inflamed colons, whereas more NK1.1(+) CD4(+) NKG2D(+) cells infiltrated into colons of mice with DSS-induced colitis...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28224362/analysis-of-foxp3-regulatory-t-cell-subpopulations-in-peripheral-blood-and-tissue-of-patients-with-systemic-lupus-erythematosus
#11
Angelika Schmidt, Cosima C Rieger, Ram Kumar Venigalla, Szabolcs Éliás, Regina Max, Hanns-Martin Lorenz, Hermann-Josef Gröne, Peter H Krammer, Annegret Kuhn
Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4(+) T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry...
February 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28223071/therapeutic-antibody-targeting-of-indoleamine-2-3-dioxygenase-ido2-inhibits-autoimmune-arthritis
#12
Lauren M F Merlo, Samantha Grabler, James B DuHadaway, Elizabeth Pigott, Kaylend Manley, George C Prendergast, Lisa D Laury-Kleintop, Laura Mandik-Nayak
Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2...
February 18, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28222511/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-aged-nzw-rabbits-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#13
Doris Lambracht-Washington, Min Fu, Mary Wight-Carter, Matthew Riegel, Roger N Rosenberg
A pathological hallmark of Alzheimer's disease (AD) are amyloid plaques in the brain consisting of aggregated amyloid-β 42 peptide (Aβ42) derived from cellular amyloid-β protein precursor (AβPP). Based on successful experiments in mouse AD models, active immunization with Aβ42 peptide and passive immunizations with anti-Aβ42 antibodies were started in clinical trials. Active Aβ42 peptide immunization in humans had led to an inflammatory autoimmune response, and the trial was stopped. Passive immunizations had shown some effects in slowing AD pathology...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222462/decreased-frequencies-of-peripheral-blood-cd4-cd25-cd127-foxp3-in-patients-with-graves-disease-and-graves-orbitopathy-enhancing-effect-of-insulin-growth-factor-1-on-treg-cells
#14
Przemyslaw Pawlowski, Kamil Grubczak, Jerzy Kostecki, Elzbieta Ilendo-Poskrobko, Marcin Moniuszko, Malgorzata Pawlowska, Robert Rejdak, Joanna Reszec, Janusz Mysliwiec
Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127(-), Foxp3) on T cells and their ability to respond to IGF-1 stimulation...
February 21, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#15
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219887/disruption-of-pathogenic-cellular-networks-by-il-21-blockade-leads-to-disease-amelioration-in-murine-lupus
#16
Jin-Young Choi, Abhinav Seth, Michael Kashgarian, Sonia Terrillon, Emma Fung, Lili Huang, Li Chun Wang, Joe Craft
Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219703/immunomodulatory-properties-of-1-2-dihydro-4-hydroxy-2-oxo-1-8-naphthyridine-3-carboxamide-derivative-vl15
#17
Anna Maria Malfitano, Chiara Laezza, Simone Bertini, Daniela Marasco, Tiziano Tuccinardi, Maurizio Bifulco, Clementina Manera
1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells (PBMC), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28218451/specific-inulin-type-fructan-fibers-protect-against-autoimmune-diabetes-by-modulating-gut-immunity-barrier-function-and-microbiota-homeostasis
#18
Kang Chen, Hao Chen, Marijke M Faas, Bart J de Haan, Jiahong Li, Ping Xiao, Hao Zhang, Julien Diana, Paul de Vos, Jia Sun
SCOPE: Dietary fibers capable of modifying gut barrier and microbiota homeostasis, affect the progression of type 1 diabetes (T1D). Here we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in non-obese diabetic (NOD) mice. METHODS AND RESULTS: Female NOD mice were weaned to long and short chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks...
February 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28216674/ccr7-deficient-inflammatory-dendritic-cells-are-retained-in-the-central-nervous-system
#19
Benjamin D Clarkson, Alec Walker, Melissa G Harris, Aditya Rayasam, Martin Hsu, Matyas Sandor, Zsuzsanna Fabry
Dendritic cells (DC) accumulate in the CNS during neuroinflammation, yet, how these cells contribute to CNS antigen drainage is still unknown. We have previously shown that after intracerebral injection, antigen-loaded bone marrow DC migrate to deep cervical lymph nodes where they prime antigen-specific T cells and exacerbate experimental autoimmune encephalomyelitis (EAE) in mice. Here, we report that DC migration from brain parenchyma is dependent upon the chemokine receptor CCR7. During EAE, both wild type and CCR7-/- CD11c-eYFP cells infiltrated into the CNS but cells that lacked CCR7 were retained in brain and spinal cord while wild type DC migrated to cervical lymph nodes...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216655/a-novel-thymoma-associated-autoimmune-disease-anti-pit-1-antibody-syndrome
#20
Hironori Bando, Genzo Iguchi, Yasuhiko Okimura, Yukiko Odake, Kenichi Yoshida, Ryusaku Matsumoto, Kentaro Suda, Hitoshi Nishizawa, Hidenori Fukuoka, Atsuko Mokubo, Katsuyoshi Tojo, Yoshimasa Maniwa, Wataru Ogawa, Yutaka Takahashi
Anti-PIT-1 antibody syndrome has recently been reported and characterized by acquired growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies associated with autoimmunity to a pituitary specific transcription factor PIT-1, which plays an essential role in GH-, PRL-, and TSH-producing cells. Although circulating anti-PIT-1 antibody and PIT-1-reactive cytotoxic T cells (CTLs) were detected in the patients, the pathophysiology and precise mechanisms for the autoimmunity remain unclarified...
February 20, 2017: Scientific Reports
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