Autoimmunity
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The autoimmune condition Hashimoto's thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. ⋯ There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells - an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto's thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto's thyroiditis.
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Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. ⋯ Interestingly, both AT-ASCs and Sc-ASCs cause increase of IL-17A secretion by activated PBMCs as well as induce up-regulation of IL-6 concentration in co-culture supernatants. We demonstrated that AT-ASCs and Sc-ASCs obtained from RA patients possess similar immunomodulatory properties despite different localization and distinct cytokine milieu of tissue of origin. Our results indicate that ASCs derived from rheumatoid adipose tissues are not strongly immunosuppressive in vitro and that they may contribute to the pathogenesis of RA due to IL-17A secretion enhancement.
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Myeloid-derived suppressor cells (MDSCs) encompass a novel population of suppressor cells and a potential candidate for cell-based therapies in inflammatory diseases. Herein, we investigated their immunomodulatory properties in experimental inflammatory colitis and T cell-mediated immune responses in inflammatory bowel disease (IBD) patients. ⋯ Our findings demonstrate an aberrant function of MDSCs in experimental inflammatory colitis and in IBD-associated immune responses in vitro. Delineation of the mechanisms that underlie the loss of MDSCs function in IBD may provide novel therapeutic targets.
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Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in the TMEM173 gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs. ⋯ Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of the TMEM173 gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, as TMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway.
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In the past, there were no studies to evaluate the incidence of Sjogren's syndrome and its relationship with sex and age in patients with systemic sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and 6485 controls from Taiwan's Registry of Catastrophic Illness database and National Health Insurance Research Database. Every patient with systemic sclerosis was matched to at most three controls by sex, age, month, and year of first diagnosis of systemic sclerosis. ⋯ Age at diagnosis of Sjogren's syndrome was earlier in patients with systemic sclerosis in both male and female groups (p = 0.018; p < 0.001, respectively). Systemic sclerosis was associated with Sjogren's syndrome after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI = 4.79-7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk alleles were all potential causes of increased incidence of Sjogren's syndrome in systemic sclerosis.