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Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells.

ABSTRACT: Mesenchymal stem cells (MSCs) possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA) patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on proliferation of peripheral blood mononuclear cells (PBMCs) and distribution of specific CD4(+) T cell subtypes (Th17, Treg, and Tfh cells) were investigated. RA MSCs appeared to be indistinguishable from controls in suppressing PBMC proliferation, decreasing the proportion of Tfh cells, and inducing the polarization of Treg cells. However, the capacity to inhibit Th17 cell polarization was impaired in RA MSCs, which was related to the low expression of CCL2 in RA MSCs after coculture with CD4(+) T cells. These findings indicated that RA MSCs display defects in several important biological activities, especially the capacity to inhibit Th17 cell polarization. These functionally impaired MSCs may contribute to the development of RA disease.

SUBMITTER: Sun Y

PROVIDER: S-EPMC4397051 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells.

Sun Yue Y Deng Wei W Geng Linyu L Zhang Lu L Liu Rui R Chen Weiwei W Yao Genhong G Zhang Huayong H Feng Xuebing X Gao Xiang X Sun Lingyun L

Journal of immunology research 20150331

Mesenchymal stem cells (MSCs) possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA) patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on prolife ...[more]

PMID: 25918734

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Project description:Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)?, IL-1? and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway.We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide ?-defensin 2 (BD2) in saliva.Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P?=?0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P?=?0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P?=?0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P?=?0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P?=?0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P?=?0.70).RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a strongly Th17-dependent opportunistic pathogen, despite an overall elevated baseline production of IL-17A.

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Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells.

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Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells.

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