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Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated from Joints of Rheumatoid Arthritis Patients
Published on: October 16, 2016
Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells
Yue Sun1, Wei Deng1, Linyu Geng1
1Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
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.
Insights
Bone marrow mesenchymal stem cells (MSCs) from rheumatoid arthritis (RA) patients exhibit impaired function. RA MSCs show reduced ability to inhibit Th17 cell polarization, potentially contributing to RA pathogenesis.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Mesenchymal stem cells (MSCs) have immunomodulatory properties and are implicated in immune-related diseases.
- Rheumatoid arthritis (RA) is an immune-related disease where MSC dysfunction may play a role.
Purpose of the Study:
- To investigate the functional characteristics of bone marrow MSCs from RA patients.
- To assess the immunomodulatory effects of RA MSCs on T cell subtypes and peripheral blood mononuclear cells (PBMCs).
Main Methods:
- Comparison of proliferative and migratory capacities of MSCs from RA patients and healthy controls.
- Analysis of cytokine profiles in RA and control MSCs.
- Co-culture experiments to evaluate the effects of RA MSCs on PBMC proliferation and CD4(+) T cell polarization (Th17, Treg, Tfh).
- Assessment of CCL2 expression in MSCs after co-culture.
Main Results:
- RA MSCs demonstrated decreased proliferation and aberrant migration compared to controls.
- No significant differences in cytokine profiles were observed between RA and control MSCs.
- RA MSCs showed impaired ability to inhibit Th17 cell polarization, linked to reduced CCL2 expression, while other immunomodulatory functions (PBMC proliferation, Tfh, Treg) were comparable to controls.
Conclusions:
- Bone marrow MSCs from RA patients exhibit functional defects, particularly in inhibiting Th17 cell polarization.
- These impaired MSC functions may contribute to the pathogenesis of rheumatoid arthritis.
- Targeting MSC dysfunction could be a potential therapeutic strategy for RA.
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