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Treg autoimmunity

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https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#1
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28318800/autoimmune-disease-development-based-on-possible-mislocalization-of-intracellular-and-extracellular-proteins
#2
Borros Arneth
BACKGROUND: T helper cells can differentiate into several subsets of T lymphocytes, including Th1, Th2, and regulatory T (Treg) cells. As a result of this ability to differentiate, the corresponding T cell receptor (TCR) spectra display considerable cellular plasticity and interchangeability. In contrast, T lymphocyte differentiation and separation into CD4(+) and/or CD8(+) T cell lines creates stable populations over a person's lifetime, which abrogates the plasticity and interchange between these cell types and their corresponding TCR spectra but results in considerable stability regarding the corresponding TCR sequences and spectra...
February 27, 2017: Immunobiology
https://www.readbyqxmd.com/read/28300523/assessment-of-th17-treg-cells-and-th-cytokines-in-an-improved-immune-thrombocytopenia-mouse-model
#3
Guoyang Zhang, Ping Zhang, Hongyun Liu, Xiaoyan Liu, Shuangfeng Xie, Xiuju Wang, Yudan Wu, Jianxing Chang, Liping Ma
OBJECTIVES: The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the human inflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model. METHODS: We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry...
March 16, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28295248/t-regulatory-cells-are-critical-for-the-maintenance-anamnestic-expansion-and-protection-elicited-by-vaccine-induced-cd8-t-cells
#4
Mitra Bhattacharyya, Pablo Penaloza MacMaster
T regulatory cells (Tregs) are critical for preventing autoimmunity and suppressing immune responses during cancer and chronic infection. However, the role of Tregs in the generation of vaccine-induced immune memory remains ill-defined. Using the mouse model of lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate that transient absence of Tregs during effector to memory CD8 T cell transition results in a permanent impairment in the maintenance, function, and recall capacity of CD8 T cells. Memory CD8 T cells in mice that were transiently depleted of Tregs exhibited defective upregulation of memory markers with a significant decrease in polyfunctionality...
March 14, 2017: Immunology
https://www.readbyqxmd.com/read/28288184/cd73-is-expressed-by-inflammatory-th17-cells-in-experimental-autoimmune-encephalomyelitis-but-does-not-limit-differentiation-or-pathogenesis
#5
Gerard Hernandez-Mir, Mandy J McGeachy
CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine, thus inhibiting inflammation. TGFβ-mediated CD73 expression on 'regulatory' Th17 cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be inflammatory in Crohn's disease. CD73 has previously been reported to contribute to inflammation in the central nervous system (CNS). In experimental autoimmune encephalomyelitis (EAE), we found that inflammatory cytokine-producing Th17 cells showed increased CD73 expression as disease progressed...
2017: PloS One
https://www.readbyqxmd.com/read/28284938/human-il-6r-hi-tigit-cd4-cd127-low-cd25-t-cells-display-potent-in-vitro-suppressive-capacity-and-a-distinct-th17-profile
#6
Ricardo C Ferreira, Daniel B Rainbow, Arcadio Rubio García, Marcin L Pekalski, Linsey Porter, João J Oliveira, Frank Waldron-Lynch, Linda S Wicker, John A Todd
To date many clinical studies aim to increase the number and/or fitness of CD4(+)CD127(low)CD25(+) regulatory T cells (Tregs) in vivo to harness their regulatory potential in the context of treating autoimmune disease. Here, we sought to define the phenotype and function of Tregs expressing the highest levels of IL-6 receptor (IL-6R). We have identified a population of CD4(+)CD127(low)CD25(+) TIGIT(-) T cells distinguished by their elevated IL-6R expression that lacked expression of HELIOS, showed higher CTLA-4 expression, and displayed increased suppressive capacity compared to IL-6R(hi)TIGIT(+) Tregs...
March 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28283756/dopamine-t-cells-and-multiple-sclerosis-ms
#7
REVIEW
Mia Levite, Franca Marino, Marco Cosentino
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others...
March 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28283017/forkhead-box-transcription-factor-1-affects-the-apoptosis-of-natural-regulatory-t-cells-by-controlling-aven-expression
#8
Zhitao Cai, Hong Liu, Xiongfei Wu
BACKGROUND: Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7Rα(CD127) are closely related to the homeostasis of Treg cells. However, the mechanism underlying Treg proliferation and activation remains unclear. Here, we evaluated how the over-expression of Foxo1 affects Treg cell proliferation via intracellular signaling. nTreg cells were transfected separately with Foxo1 and Aven small-interfering RNA (siRNA) or over-expression plasmid...
March 10, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28282791/anti-arthritic-effect-of-berberine-on-adjuvant-induced-rheumatoid-arthritis-in-rats
#9
Xue Wang, Xin He, Chun-Feng Zhang, Chang-Run Guo, Chong-Zhi Wang, Chun-Su Yuan
BACKGROUND: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease, which affects approximately 1% adult population in the worldwide. AIM: The present study was to investigate the anti-arthritic effect of berberine and its involved mechanism in Freund's complete adjuvant (FCA) induced arthritis rats. METHODS AND MATERIALS: Rats were divided randomly into control, FCA, tripterysium glycosides, berberine (75 and 150mg/kg). The apparent indicators, including changes of body weights, paw swelling degrees and arthritis indexes, were analyzed to evaluate anti-arthritic effect of berberine...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28271325/nebulization-of-rns60-a-physically-modified-saline-attenuates-the-adoptive-transfer-of-experimental-allergic-encephalomyelitis-in-mice-implications-for-multiple-sclerosis-therapy
#10
Susanta Mondal, Suresh B Rangasamy, Supurna Ghosh, Richard L Watson, Kalipada Pahan
Developing a new and effective therapeutic approach against multiple sclerosis (MS) is always an important area of research. RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60, administered through intraperitoneal injection, ameliorated clinical symptoms and disease progression of experimental allergic encephalomyelitis (EAE), an animal model of MS. Since the intravenous route is not preferred for treating a chronic condition, we tested if nebulization of RNS60 could attenuate the disease process of adoptively-transferred EAE in mice...
March 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28270700/growth-arrest-specific-6-enhances-the-suppressive-function-of-cd4-cd25-regulatory-t-cells-mainly-through-axl-receptor
#11
Guang-Ju Zhao, Jia-Yi Zheng, Jia-Lan Bian, Long-Wang Chen, Ning Dong, Yan Yu, Guang-Liang Hong, Arvine Chandoo, Yong-Ming Yao, Zhong-Qiu Lu
Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28264971/the-lower-limit-of-regulatory-cd4-foxp3-tcr%C3%AE-repertoire-diversity-required-to-control-autoimmunity
#12
Aixin Yu, Michael J Dee, Dennis Adeegbe, Connor J Dwyer, Norman H Altman, Thomas R Malek
The TCR repertoire of regulatory T cells (Tregs) is highly diverse. The relevance of this diversity to maintain self-tolerance remains unknown. We established a model where the TCR repertoire of normal polyclonal Tregs was limited by serial transfers into IL-2Rβ(-/-) mice, which lack functional Tregs. After a primary transfer, the donor Treg TCR repertoire was substantially narrowed, yet the recipients remained autoimmune-free. Importantly, upon purification and transfer of donor-derived Tregs from an individual primary recipient into neonatal IL-2Rβ(-/-) mice, the secondary recipients developed autoimmunity...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28261223/regulatory-b-cells-in-pregnancy-lessons-from-autoimmunity-graft-tolerance-and-cancer
#13
REVIEW
Ruth Marian Guzman-Genuino, Kerrilyn R Diener
The success of pregnancy is contingent on the maternal immune system recognizing and accommodating a growing semi-allogeneic fetus. Specialized subsets of lymphocytes capable of negative regulation are fundamental in this process, and include the regulatory T cells (Tregs) and potentially, regulatory B cells (Bregs). Most of our current understanding of the immune regulatory role of Bregs comes from studies in the fields of autoimmunity, transplantation tolerance, and cancer biology. Bregs control autoimmune diseases and can elicit graft tolerance by inhibiting the differentiation of effector T cells and dendritic cells (DCs), and activating Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28259000/th17-treg-imbalance-and-increased-interleukin-21-are-associated-with-liver-injury-in-patients-with-chronic-severe-hepatitis-b
#14
Bin Liu, Wei Gao, Li Zhang, Jing Wang, Min Chen, Mingli Peng, Hong Ren, Peng Hu
BACKGROUND: Th17/Treg imbalance and the levels of related cytokines are essential in the pathogenesis of autoimmune and infectious diseases. The aim of the current study was to assess the Treg/Th17 balance and the levels of related cytokines associated with various degrees of liver injury in patients with chronic hepatitis B virus (HBV) infection. METHODS: The proportions of peripheral Th17, Treg and Th1 cells in 7 patients classified as asymptomatic hepatitis B virus carriers (AsCs), 38 patients with low or moderate grade chronic hepatitis B (CHB-LM), 20 patients with chronic severe hepatitis B (CSHB), and 10 healthy controls (HCs) were determined by flow cytometry...
March 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28258292/immunoregulatory-properties-of-the-cytokine-il-34
#15
REVIEW
Carole Guillonneau, Séverine Bézie, Ignacio Anegon
Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation...
March 3, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28257995/regulatory-b-cells-phenotype-function-and-role-in-transplantation
#16
REVIEW
C M Wortel, S Heidt
While B cells are traditionally known for their roles in antibody production, antigen presentation and cytokine production, recent studies have highlighted the existence of B cells with regulatory properties, which have been termed Bregs, analogous to regulatory T cells (Tregs). Bregs have been found to play a role in autoimmune disease, malignancies, infections, and may also be involved in solid organ transplantation. Their main mechanism of action is by promoting the development of Tregs while suppressing effector CD4(+) and CD8(+) T cells, primarily by IL-10 secretion...
March 1, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28257599/immunosuppressive-drugs-affect-ifn%C3%AE-and-pd1-kinetics-in-patients-with-newly-diagnosed-autoimmune-hepatitis
#17
Charlotte R Grant, Beth S Holder, Rodrigo Liberal, Michael A Heneghan, Yun Ma, Giorgina Mieli-Vergani, Diego Vergani, Maria Serena Longhi
Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs). Several lines of evidence indicate CD4 as the main effectors involved in the autoimmune liver damage. Herein we investigate the in vitro effects of prednisolone, 6-mercaptopurine, cyclosporine, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of pro-inflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4(+) CD25(-) cells, isolated from the peripheral blood of treatment-naïve patients with AIH...
March 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28257518/exposure-to-sequestered-self-antigens-in-vivo-is-not-sufficient-for-the-induction-of-autoimmune-diabetes
#18
Nobuyuki Ono, Kiichi Murakami, Olivia Chan, Håkan Hall, Alisha R Elford, Patty Yen, Thomas Calzascia, David M Spencer, Pamela S Ohashi, Salim Dhanji
Although the role of T cells in autoimmunity has been explored for many years, the mechanisms leading to the initial priming of an autoimmune T cell response remain enigmatic. The 'hit and run' model suggests that self-antigens released upon cell death can provide the initial signal for a self-sustaining autoimmune response. Using a novel transgenic mouse model where we could induce the release of self-antigens via caspase-dependent apoptosis. We tracked the fate of CD8+ T cells specific for the self-antigen...
2017: PloS One
https://www.readbyqxmd.com/read/28251714/the-transdifferentiation-of-regulatory-t-and-th17-cells-in-autoimmune-inflammatory-diseases-and-its-potential-implications-in-pregnancy-complications
#19
Zhao-Zhao Liu, Guo-Qiang Sun, Xiao-Hui Hu, Joanne Kwak-Kim, Ai-Hua Liao
In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases...
March 2, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28248972/novel-cd28-antagonist-mpeg-pv1-fab-mitigates-experimental-autoimmune-uveitis-by-suppressing-cd4-t-lymphocyte-activation-and-ifn-%C3%AE-production
#20
Pedro Henrique Papotto, Eliana Blini Marengo, Luiz Roberto Sardinha, Karina Inácio Carvalho, Ana Eduarda Zulim de Carvalho, Sheyla Castillo-Mendez, Carina Calixto Jank, Bernard Vanhove, Anna Carla Goldberg, Luiz Vicente Rizzo
Autoimmune Uveitis is an important chronic inflammatory disease and a leading cause of impaired vision and blindness. This ocular autoimmune disorder is mainly mediated by T CD4+ lymphocytes poising a TH1 phenotype. Costimulatory molecules are known to play an important role on T cell activation and therefore represent interesting therapeutical targets for autoimmune disorders. CD28 is the prototypical costimulatory molecule for T lymphocytes, and plays a crucial role in the initiation, and maintenance of immune responses...
2017: PloS One
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