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Treg multiple sclerosis

Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Annukka Pietikäinen, Mikael Maksimow, Tommi Kauko, Saija Hurme, Marko Salmi, Jukka Hytönen
BACKGROUND: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods...
October 18, 2016: Journal of Neuroinflammation
Elisabetta Volpe, Manolo Sambucci, Luca Battistini, Giovanna Borsellino
Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens...
2016: Frontiers in Immunology
Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li
Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords...
October 15, 2016: Journal of Neuroimmunology
Carine Savarin, Cornelia C Bergmann, David R Hinton, Stephen A Stohlman
Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells...
2016: Frontiers in Immunology
Hongna Yang, Jinhua Sun, Feng Wang, Yan Li, Jianzhong Bi, Tingyu Qu
The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs...
September 29, 2016: Oncotarget
Oscar Ka-Fai Ma, Koon Ho Chan
Mesenchymal stem cells (MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T (Treg) and B (Breg) cells...
September 26, 2016: World Journal of Stem Cells
Marco Cosentino, Mauro Zaffaroni, Massimiliano Legnaro, Raffaella Bombelli, Laura Schembri, Damiano Baroncini, Anna Bianchi, Raffaella Clerici, Mario Guidotti, Paola Banfi, Giorgio Bono, Franca Marino
Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients...
September 15, 2016: Journal of Neuroimmunology
Madhuchhanda Kundu, Susanta Mondal, Avik Roy, Jeffrey L Martinson, Kalipada Pahan
Upregulation and/or maintenance of regulatory T cells (Tregs) during autoimmune insults may have therapeutic efficacy in autoimmune diseases. Earlier we have reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders, upregulates Tregs and protects mice from experimental allergic encephalomyelitis, an animal model of multiple sclerosis. However, mechanisms by which NaB increases Tregs are poorly understood. Because TGF-β is an important inducer of Tregs, we examined the effect of NaB on the status of TGF-β...
September 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Aref Hosseini, Kamran Ghaedi, Somayeh Tanhaei, Mazdak Ganjalikhani-Hakemi, Shohreh Teimuri, Masoud Etemadifar, Mohammad Hossein Nasr Esfahani
OBJECTIVE: MicroRNAs (miRNA) are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis (MS). Th17 and regulatory T (Treg) cells are two subsets of CD4+T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish fluctuations in expression of CD4+T-cell derived miR-223 during the relapsing-remitting (RR) phase of MS (RR-MS), as well as the expressions of Th17 and Treg cell markers...
2016: Cell Journal
Alexander Ulges, Esther J Witsch, Gautam Pramanik, Matthias Klein, Katharina Birkner, Ulrike Bühler, Beatrice Wasser, Felix Luessi, Natascha Stergiou, Sarah Dietzen, Till-Julius Brühl, Toszka Bohn, Georg Bündgen, Horst Kunz, Ari Waisman, Hansjörg Schild, Edgar Schmitt, Frauke Zipp, Tobias Bopp
T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Pingxia Lu, Yingping Cao, Meihua Wang, Peizheng Zheng, Juan Hou, Chanhong Zhu, Jianda Hu
Multiple sclerosis (MS) is generally acknowledged to be an autoimmune disease, but its etiology remains unknown. The most intensively studied animal model of MS is experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs), the professional antigen presenting cells (APCs), have gained increasing attention because they connect innate and adaptive immunity. The aim of this study was to determine the role of mature DCs in the pathogenesis of EAE. It was found that the number of mature DCs in the EAE spleen increased compared to the control group (p < 0...
2016: Central-European Journal of Immunology
Jinlong Jian, Guangfei Li, Aubryanna Hettinghouse, Chuanju Liu
Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of Treg differentiation and IL-10 expression and inhibition of chemokine release from macrophages...
August 12, 2016: Cytokine
Javier Ochoa-Repáraz, Lloyd H Kasper
There is considerable interest in trying to understand the importance of the gut microbiome in human diseases. The association between dysbiosis, an altered microbial composition, as related to human disease is being explored in the context of different autoimmune conditions, including multiple sclerosis (MS). Recent studies suggest that MS affects the composition of the gut microbiota by altering the relative abundances of specific bacteria and archaea species. Remarkably, some of the bacterial species shown reduced in the gut of MS patients are known to promote immunosuppressive regulatory T cells (Tregs)...
July 28, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Abdullah Alsuliman, Stanley H Appel, David R Beers, Rafet Basar, Hila Shaim, Indresh Kaur, Jane Zulovich, Eric Yvon, Muharrem Muftuoglu, Nobuhiko Imahashi, Kayo Kondo, Enli Liu, Elizabeth J Shpall, Katayoun Rezvani
Regulatory T cells (Tregs) play a fundamental role in the maintenance of self-tolerance and immune homeostasis. Defects in Treg function and/or frequencies have been reported in multiple disease models. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Compelling evidence supports a neuroprotective role for Tregs in this disease. Indeed, rapid progression in ALS patients is associated with decreased FoxP3 expression and Treg frequencies...
October 2016: Cytotherapy
Yanwen Xu, Zhongze He, Zhaoying Li, Shaohong Fang, Yun Zhang, Cong Wan, Yiming Ma, Peng Lin, Chuanliang Liu, Guangyou Wang, Rui Li, Jiwei Zhu, Ying Li, Lili Mu, Yao Zhang, Jinghua Wang, Qingfei Kong, Hulun Li, Bo Sun
The classically activated (M1) macrophage has been shown to play an indispensable role in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). However, most studies focus on the effect of macrophage on CNS demyelination of EAE; whether the M1 macrophage participates in early EAE and the molecular mechanism underlying remains unclear. Here, we showed that the immunity-related GTPase family member 1 (Irgm1), also known as LRG-47, was expressed in M1 macrophages of draining lymph nodes (dLNs) from C57BL/6 mice with early EAE, and the IRGM1 heterozygote substantially reduced M1 macrophage accumulation in dLNs and spleen of the primary EAE stage...
July 21, 2016: Journal of Leukocyte Biology
Gelena V Lifshitz, Dmitry D Zhdanov, Anastasia V Lokhonina, Daria D Eliseeva, Elena Y Lyssuck, Igor A Zavalishin, Svetlana N Bykovskaia
Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4(+)CD25(+) T cells. We demonstrated difference in proportion of regulatory T cells CD4(+)CD25(+)FoxP3(+)CD127(low) (Tregs) within the same patients' relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients' remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors...
July 16, 2016: Autoimmunity
Melanie Keil, Jana K Sonner, Tobias V Lanz, Iris Oezen, Theresa Bunse, Stefan Bittner, Hannah V Meyer, Sven G Meuth, Wolfgang Wick, Michael Platten
Relapsing-remitting multiple sclerosis (MS)(2) is characterized by phases of acute neuroinflammation followed by spontaneous remission. Termination of inflammation is accompanied by an influx of regulatory T cells (Tregs).(3) The molecular mechanisms responsible for directing Tregs into the inflamed CNS tissue, however, are incompletely understood. In an MS mouse model we show that the stress kinase general control non-derepressible 2 (GCN2),(4) expressed in T cells, contributes to the resolution of autoimmune neuroinflammation...
August 15, 2016: Journal of Neuroimmunology
Sharee A Basdeo, Siobhan Kelly, Karen O'Connell, Niall Tubridy, Christopher McGuigan, Jean M Fletcher
BACKGROUND: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation...
2016: SpringerPlus
Adel Mohammadzadeh, Ali Akbar Pourfathollah, Somayeh Shahrokhi, Ali Fallah, Mohammad Taher Tahoori, Afshin Amari, Mahdi Forouzandeh, Masoud Soleimani
Interferon-β (IFN-β) is commonly used as a disease modifying drug for the treatment of relapse-remitting multiple sclerosis (RR-MS). However, the underlying mechanism by which IFN-β mediate this immunosuppressive effect is still unknown. In this study, we analyzed the effects of genetically modified adipose-derived mesenchymal stem cells (AD-MSCs) expressing murine interferon beta (MSCs-VP/IFN-β) on the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Lymph node mononuclear cells and serum were examined by using RT-PCR and ELISA methods to measure the production of IL-10 and IL-17 gene and protein expression, respectively...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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