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Treg autoimmunity

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https://www.readbyqxmd.com/read/28225165/the-contrasting-role-of-th17-immunity-in-human-health-and-disease
#1
Edwin Hoe, Jeremy Anderson, Jordan Nathanielsz, Zheng Quan Toh, Rachel Marimla, Anne Balloch, Paul V Licciardi
The human immune system is a tightly regulated network that protects the host from disease. An important aspect of this is the balance between pro-inflammatory Th17 cells and anti-inflammatory Treg cells in maintaining immune homeostasis. Foxp3+ Treg are critical for sustaining immune tolerance through IL-10 and TGF-β while RORγt+ Th17 cells promote immunopathology and auto-inflammatory diseases through the actions of IL-17A, IL-21 and IL-22. Therefore, the imbalance between Treg and Th17 cells can result in serious pathology in many organs and tissues in the body...
February 22, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28224362/analysis-of-foxp3-regulatory-t-cell-subpopulations-in-peripheral-blood-and-tissue-of-patients-with-systemic-lupus-erythematosus
#2
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/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
#3
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/28218625/egress-of-sperm-autoantigen-from-seminiferous-tubules-maintains-systemic-tolerance
#4
Kenneth S K Tung, Jessica Harakal, Hui Qiao, Claudia Rival, Jonathan C H Li, Alberta G A Paul, Karen Wheeler, Patcharin Pramoonjago, Constance M Grafer, Wei Sun, Robert D Sampson, Elissa W P Wong, Prabhakara P Reddi, Umesh S Deshmukh, Daniel M Hardy, Huanghui Tang, C Yan Cheng, Erwin Goldberg
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218451/specific-inulin-type-fructan-fibers-protect-against-autoimmune-diabetes-by-modulating-gut-immunity-barrier-function-and-microbiota-homeostasis
#5
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/28216262/efis-lecture-understanding-the-ctla-4-checkpoint-in-the-maintenance-of-immune-homeostasis
#6
REVIEW
Lucy S K Walker
The past 20 years have heralded fascinating developments in the field of CTLA-4 biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and its absence provokes severe lymphoproliferative disease. In a surprising twist, the generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell can modify the behaviour of another cell. This was followed by the demonstration that CTLA-4 is highly expressed in regulatory T cells and can contribute to their suppressive activity...
February 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28215223/the-functional-stability-of-foxp3-and-ror%C3%AE-t-in-treg-and-th17-and-their-therapeutic-applications
#7
J Ren, B Li
The balance of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) and effector T cells plays a key role in maintaining immune homeostasis, while the imbalance of them is related to many inflammatory diseases in both human and mice. Here we discuss about the plasticity of Tregs and Th17 cells, and the related human diseases resulted from the imbalance of them. Further, we will focus on the mechanisms regulating the plasticity between Tregs and Th17 cells and the potential therapeutic strategies by targeting regulators of the expression and activity of FOXP3 and RORγt or regulators of Treg/Th17 balance in autoimmune diseases, allergy, infection, and cancer...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#8
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28211077/severe-bullous-pemphigoid-associated-with-pembrolizumab-therapy-for-metastatic-melanoma-with-complete-regression
#9
O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
February 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28207428/il-37-ameliorates-coxsackievirus-b3-induced-viral-myocarditis-by-modulating-the-th17-treg-immune-response
#10
Bang An, Xuefei Liu, Ge Li, Haitao Yuan
Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle with an excessively activated immune response. Numerous interventions have been investigated for the treatment of myocarditis while success is limited. Interleukin-37 (IL-37), a novel member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. However, the modulatory effect of IL-37 in myocarditis is unknown. In this study, we investigated the immunological regulation of IL-37 in the coxsackievirus B3-induced model of murine viral myocarditis...
February 14, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28205558/plant-based-vaccines-for-oral-delivery-of-type-1-diabetes-related-autoantigens-evaluating-oral-tolerance-mechanisms-and-disease-prevention-in-nod-mice
#11
Amanda L Posgai, Clive H Wasserfall, Kwang-Chul Kwon, Henry Daniell, Desmond A Schatz, Mark A Atkinson
Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3(+) and LAP(+) regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199204/the-crossroads-between-cancer-immunity-and-autoimmunity-antibodies-to-self-antigens
#12
Monica Benvenuto, Rosanna Mattera, Laura Masuelli, Ilaria Tresoldi, Maria Gabriella Giganti, Giovanni Vanni Frajese, Vittorio Manzari, Andrea Modesti, Roberto Bei
The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198408/therapeutic-effects-of-human-adipose-tissue-derived-stem-cell-hadsc-transplantation-on-experimental-autoimmune-encephalomyelitis-eae-mice
#13
Jia Li, Ying Chen, Zhibo Chen, Yuanyuan Huang, Dehao Yang, Zhongqian Su, Yiyun Weng, Xiang Li, Xu Zhang
This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193225/the-active-metabolite-of-leflunomide-a77-1726-attenuates-inflammatory-arthritis-in-mice-with-spontaneous-arthritis-via-induction-of-heme-oxygenase-1
#14
Su-Jin Moon, Eun-Kyung Kim, Joo Yeon Jhun, Hee Jin Lee, Weon Sun Lee, Sang-Hi Park, Mi-La Cho, Jun-Ki Min
BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28191643/cd11b-regulates-via-il-6-the-treg-th17-balance-in-murine-arthritis
#15
Mathias Stevanin, Nathalie Busso, Veronique Chobaz, Matteo Pigni, Sahar Ghassem-Zadeh, Li Zhang, Hans Acha-Orbea, Driss Ehirchiou
Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b(-/-) mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA)-induced arthritis. C57BL/6 and CD11b(-/-) resistant mice were immunized with type II collagen. CD11b(-/-) mice developed arthritis with early onset, high incidence and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b(-/-) mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration...
February 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#16
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176332/low-dose-interleukin-2-promotes-stat5-phosphorylation-treg-survival-and-ctla-4-dependent-function-in-autoimmune-liver-diseases
#17
Hannah C Jeffery, Louisa E Jeffery, Philipp Lutz, Margaret Corrigan, Gwilym J Webb, Gideon M Hirschfield, David H Adams, Ye Htun Oo
CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and regulatory T cells contribute to the pathogenesis of autoimmune diseases. We recently reported that the hepatic microenvironment is deficient in IL-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate STAT5 phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases...
February 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28170174/transplantation-of-donor-origin-mouse-embryonic-stem-cell-derived-thymic-epithelial-progenitors-prevents-the-development-of-chronic-graft-versus-host-disease-in-mice
#18
Rong Hu, Yalan Liu, Min Su, Yinhong Song, Debra Rood, Laijun Lai
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft-versus-host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T-cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#19
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167605/thymus-derived-treg-cell-development-is-regulated-by-c-type-lectin-mediated-bic-mirna155-expression
#20
Raquel Sánchez-Díaz, Rafael Blanco-Dominguez, Sandra Lasarte, Katerina Tsilingiri, Enrique Martín-Gayo, Beatriz Linillos-Pradillo, Hortensia de la Fuente, Francisco Sánchez-Madrid, Rinako Nakagawa, María L Toribio, Pilar Martín
Thymus-derived regulatory T cells (tTregs) are key to prevent autoimmune diseases but the mechanisms involved in their development remain unsolved. Here, we show that the C-type lectin receptor CD69 controls tTreg cell development and peripheral Treg homeostasis through the regulation of BIC/miR-155 and its target, the suppressor of cytokine signaling 1 (SOCS-1). Using Foxp3-mRFP/cd69(+/-) or/cd69(-/-) reporter mice, shRNA-mediated silencing and miR-155 transfection approaches, we found that CD69 deficiency impaired the signal transducer and activator of transcription 5 (STAT5) pathway in Foxp3(+) cells...
February 6, 2017: Molecular and Cellular Biology
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