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Treg autoimmunity

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https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#1
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442414/inhibition-of-allogeneic-cytotoxic-t-cell-cd8-proliferation-via-polymer-induced-treg-cd4-cells
#2
Ning Kang, Wendy M Toyofuku, Xining Yang, Mark D Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8(+)) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8(+) and CD4(+) alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model...
April 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28440511/simultaneously-increased-expression-of-glucocorticoid%C3%A2-induced-tumor-necrosis-factor-receptor-and-its-ligand-contributes-to-increased-interleukin%C3%A2-5-13%C3%A2-producing-group-2-innate-lymphocytes-in-murine-asthma
#3
Mengying Zhang, Jie Wan, Yunyun Xu, Danyi Zhang, Jingjing Peng, Chen Qi, Qi Guo, Sheng Xia, Zhaoliang Su, Shengjun Wang, Huaxi Xu
Glucocorticoid‑induced tumor necrosis factor receptor (GITR) is expressed at high levels on CD4+CD25+ regulatory T cells (Tregs). Following activation by its ligand (GITRL), GITR influences the activity of effector T cells and Tregs and participates in the development of numerous autoimmune and inflammatory diseases, including asthma. However, the GITR/GITRL expression level in lung tissue and its influence on group 2 innate lymphocytes (ILC2s) in asthma remains unclear. The present study detected the number of ILC2s and the expression levels of GITR and GITRL in the lung tissues of asthmatic mice by flow cytometry analysis, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440200/effect-of-halofuginone-on-the-pathogenesis-of-autoimmune-thyroid-disease-in-different-mice-models
#4
Xin Hou, Jin Zhou, Rong Yang, Shanshan Liu, Mei Bi, Tong Liu, Chenling Fan, Haixia Guan, Yushu Li, Zhongyan Shan, Weiping Teng
OBJECTIVE: Our objectives were to investigate the therapeutic effect of halofuginone (HF) in the treatment of autoimmune thyroid diseases (AITDs) and explore its underlying mechanism of action. METHODS: The Graves' disease (GD) model was generated by immunizing female BALB/c mice with adenovirus expressing the TSH receptor A subunit (Ad-TSHR289). The Ad-TSHRA+HF and Ad-TSHRA+DMSO groups were injected intraperitoneally with HF or the vehicle control (DMSO), respectively...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28438552/immunomodulation-of-autoimmune-arthritis-by-pro-inflammatory-cytokines
#5
REVIEW
Eugene Y Kim, Kamal D Moudgil
Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage, while anti-inflammatory cytokines help resolve inflammation and facilitate tissue repair. Over the past few decades, this general feature of cytokine-mediated events has offered a broad framework to comprehend the pathogenesis of autoimmune and other immune-mediated diseases, and to successfully develop therapeutic approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis factor-α (TNF-α) therapy is a testimony in support of this endeavor...
April 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28436428/neuronal-ifn-beta-induced-pi3k-akt-foxa1-signalling-is-essential-for-generation-of-foxa1-treg-cells
#6
Yawei Liu, Andrea Marin, Patrick Ejlerskov, Louise Munk Rasmussen, Marco Prinz, Shohreh Issazadeh-Navikas
Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28434074/adipose-derived-stem-cells-ameliorate-experimental-murine-colitis-via-tsp-1-dependent-activation-of-latent-tgf-%C3%AE
#7
Hiroshi Takeyama, Tsunekazu Mizushima, Mamoru Uemura, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Ichiro Takemasa, Masakazu Ikenaga, Kohei Murata, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
BACKGROUND: Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease. METHODS: Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally...
April 22, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28432597/t-regulatory-cells-in-bone-remodelling
#8
REVIEW
Aline Bozec, Mario M Zaiss
PURPOSE OF THE REVIEW: In this review, we present the role of regulatory T (Treg) cells in bone remodelling and bone-related disease such as osteoporosis or inflammatory bone loss. We also discuss the cellular and molecular mechanism how Treg cells regulate osteoclastogenesis. RECENT FINDINGS: Treg cells could regulate osteoclastogenesis by secreting TGF-β and IL-10 as well as IL-4 cytokines. Moreover, Treg cells can additionally regulate osteoclast differentiation, in a cell-to-cell contact via the cytotoxic T lymphocyte antigen (CTLA-4)...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28429709/t-follicular-helper-and-t-follicular-regulatory-cells-have-different-tcr-specificity
#9
Ana Raquel Maceiras, Silvia Cristina Paiva Almeida, Encarnita Mariotti-Ferrandiz, Wahiba Chaara, Fadi Jebbawi, Adrien Six, Shohei Hori, David Klatzmann, Jose Faro, Luis Graca
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429331/the-correlation-of-cd19%C3%A2-%C3%A2-cd24%C3%A2-%C3%A2-cd38%C3%A2-%C3%A2-b-cells-and-other-clinicopathological-variables-with-the-proportion-of-circulating-tregs-in-breast-cancer-patients
#10
Mohammad Kazzem Gheybi, Shokrollah Farrokhi, Mohammad Reza Ravanbod, Afshin Ostovar, Valiollah Mehrzad, Pardis Nematollahi
BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19(+)CD24(hi)CD38(hi) cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19(+)CD24(hi)CD38(hi) cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients...
April 20, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28423665/il-33-induced-alternatively-activated-macrophage-attenuates-the-development-of-tnbs-induced-colitis
#11
Lei Tu, Jie Chen, Dandan Xu, Zhongming Xie, Bing Yu, Ying Tao, Guixiu Shi, Lihua Duan
Accumulated data have shown that alternatively activated macrophage exerts a modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a critical modulator in adaptive and innate immune, has been implicated in autoimmunity and inflammation. Previously, we have reported that IL-33 functions as a protective modulator in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33 primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced colitis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423200/cd80cd86-deficiency-disrupts-regulatory-cd4-foxp3-t-cell-homeostasis-and-induces-autoimmune-like-alopecia
#12
Ji-Hyun Bae, Woo-Sung Hwang, Yoo-Jin Jang, Yoon-Hoo Lee, Da-Eun Jang, Jung-Sik Kim, Su-Cheong Yeom
Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86(-/-) ) mice. Incidence and severity of alopecia were analyzed in 58 B6.CD80CD86(-/-) mice by using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR, and CD25 inhibition test. Both male and female B6...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28421297/suppression-of-th1-differentiation-by-tryptophan-supplementation-in-vivo
#13
Tobias V Lanz, Simon Becker, Soumya R Mohapatra, Christiane A Opitz, Wolfgang Wick, Michael Platten
Metabolism of the essential amino acid tryptophan (trp) is a key endogenous immunosuppressive pathway restricting inflammatory responses. Tryptophan metabolites promote regulatory T cell (Treg) differentiation and suppress proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that treatment with natural and synthetic tryptophan metabolites can suppress autoimmune neuroinflammation in preclinical animal models. Here, we tested if oral intake of tryptophan would increase immunosuppressive tryptophan metabolites and ameliorate autoimmune neuroinflammation as a safe approach to treat autoimmune disorders like multiple sclerosis (MS)...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28416503/invariant-natural-killer-t-cells-ameliorate-murine-chronic-gvhd-by-expanding-donor-regulatory-t-cells
#14
Jing Du, Katelyn Paz, Govindarajan Thangavelu, Dominik Schneidawind, Jeanette Baker, Ryan Flynn, Omar Duramad, Colby Feser, Angela Panoskaltsis-Mortari, Robert S Negrin, Bruce R Blazar
Chronic graft-versus-host-disease (cGVHD) can cause multi-organ system disease typically with autoimmune-like features, resulting in high mortality and morbidity due to treatment limitations. Invariant natural killer T cells (iNKTs), a small population characterized by expression of a semi-invariant T-cell receptor, rapidly produce copious amounts of diverse cytokines upon activation that exert potent immune regulatory function. Here, we show that iNKTs are significantly reduced in a cGVHD murine model that recapitulates several aspects of autoimmunity and organ fibrosis observed in cGVHD patients...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28416194/foxp3-reprograms-t-cell-metabolism-to-function-in-low-glucose-high-lactate-environments
#15
Alessia Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, Matthew H Levine, Zhonglin Wang, William J Quinn, Piotr K Kopinski, Liqing Wang, Tatiana Akimova, Yujie Liu, Tricia R Bhatti, Rongxiang Han, Benjamin L Laskin, Joseph A Baur, Ian A Blair, Douglas C Wallace, Wayne W Hancock, Ulf H Beier
Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant, avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Tregs) maintain peripheral tolerance, but how Tregs function in low-glucose, lactate-rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation...
April 11, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28412855/decreased-tlr4-expression-on-monocytes-may-cause-regulatory-t-cells-abnormality-in-patients-with-primary-immune-thrombocytopenia
#16
Yating Hao, Huiyuan Li, Yang Li, Mingen Lyu, Donglei Zhang, Rongfeng Fu, Yue Guan, Shixuan Wang, Boyang Sun, Xueqing Dou, Renchi Yang
Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions including T helper type 1 cell (Th1) polarization and regulatory T cells (Tregs) deficiency. This study aimed to determine the effects of TLR4 on Treg differentiation and the cytokine production of peripheral blood mononuclear cells (PBMCs) from patients with ITP. We found that expression of TLR4 on monocytes was significantly decreased in patients with active ITP than that in healthy controls and it had positive correlation with platelet count...
April 17, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#17
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28400721/mir-384-regulates-the-th17-treg-ratio-during-experimental-autoimmune-encephalomyelitis-pathogenesis
#18
Xuebin Qu, Jingjing Han, Ying Zhang, Yuanyuan Wang, Jun Zhou, Hongbin Fan, Ruiqin Yao
Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS), during which IL-17-producing CD4(+) T helper (Th17) cells accumulate in the central nervous system (CNS). In this study, we identified levels of miR-384 as significantly increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Over-expression of miR-384 in vivo led to severe EAE, characterized by exacerbated demyelination, and increased inflammatory cell infiltration of the spinal cord; inhibition of miR-384 reversed these changes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28398870/interleukin-35-rescues-regulatory-b-cell-function-but-the-effect-is-dysregulated-in-ulcerative-colitis
#19
Shaoxuan Wang, Chengyong Qin
Ulcerative colitis (UC) is a long-time inflammatory condition arising from aberrant immune activation in the colon and the rectum. Interleukin (IL)-35 plays critical roles in autoimmune disorders. In this study, we explored the pathways of IL-35 in affecting UC. First, peripheral blood mononuclear cells (PBMCs) from UC patients were obtained. Pretreating PBMCs with IL-35 resulted in significantly elevated IL-10 production from whole PBMCs as well as B cells, whereas pretreating PBMCs with IL-12 or IL-27 did not demonstrate a similar effect...
February 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28396406/flicr-a-long-noncoding-rna-modulates-foxp3-expression-and-autoimmunity
#20
David Zemmour, Alvin Pratama, Scott M Loughhead, Diane Mathis, Christophe Benoist
A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in a subset of Tregs with twofold- to fivefold-lower levels of FoxP3 protein. The impact of Flicr is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses Flicr expression...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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