Mesenchymal stem cells negatively regulate CD4<sup>+</sup> T cell activation in patients with primary Sj&ouml;gren syndrome through the miRNA‑125b and miRNA‑155 TCR pathway

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doi:10.3892/mmr.2020.11681

Mesenchymal stem cells negatively regulate CD4⁺ T cell activation in patients with primary Sjögren syndrome through the miRNA‑125b and miRNA‑155 TCR pathway

Authors:
- Bangdong Gong
- Ling Zheng
- Zhenhao Lu
- Jiashu Huang
- Jincheng Pu
- Shengnan Pan
- Min Zhang
- Jie Liu
- Jianping Tang
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Affiliations: Division of Rheumatology, Tongji Hospital of Tongji University School of Medicine, Shanghai 200065, P.R. China, Division of Respiratory Medicine, Tongji Hospital of Tongji University School of Medicine, Shanghai 200065, P.R. China, Center for Regenerative Medicine, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
Published online on: November 10, 2020 https://doi.org/10.3892/mmr.2020.11681
Article Number: 43
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Treatment with mesenchymal stem cells (MSCs) has been revealed to suppress CD4⁺ T cells and autoimmunity in both mouse models and patients with primary Sjögren syndrome (pSS); however, the underlying mechanism remains unclear. MicroRNAs (miRNAs or miRs) mediate CD4⁺ T cell activation, but the mechanism is not understood, particularly for CD4⁺ T cells treated with MSCs. Characterization of miRNAs may reveal pSS pathogenesis, guide MSC treatment and provide more personalized management options. The present study aimed to perform an miRNome analysis of quiescent and T cell receptor (TCR)‑activated CD4⁺ T cells treated with MSCs via miRNA proﬁles and bioinformatics. Following 72 h of co‑culture, MSCs inhibited TCR‑induced CD4⁺ T cell activation and decreased IFN‑γ levels. The numbers of aberrant miRNAs in pSS naïve (vs. healthy naïve), pSS activation (vs. pSS naïve), MSC treatment and pre‑IFN‑γ MSC treatment (vs. pSS activation) groups were 42, 55, 27 and 32, respectively. Gene enrichment analysis revealed that 259 pathways were associated with CD4⁺ T cell stimulation, and 240 pathways were associated with MSC treatment. Increased miRNA‑7150 and miRNA‑5096 and decreased miRNA‑125b‑5p and miRNA‑22‑3p levels in activated CD4⁺ T cells from patients with pSS were reversed by MSC treatment. Notably, the proliferation of CD4⁺ T cells and CD4⁺ IFN‑γ⁺ cells, expression levels of miRNA‑125b‑5p and miRNA‑155 in CD4⁺ T cells and supernatant IFN‑γ secretion were associated with disease activity. miRNA may play a vital role in MSC treatment for activated CD4⁺ T cells. The results indicated that the expression levels of miRNA‑125b‑5p and miRNA‑155 in TCR‑activated CD4⁺ T cells from patients with pSS may provide insight regarding autoimmune diseases and offer a novel target for prospective treatment. Therefore, these results may be crucial in providing MSC treatment for pSS.

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