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Preprints

Mesenchymal stem cell enhances the function of MDSCs in experimental Sjögren syndrome mice

Tian J, Hong Y, Zhu Q, Zhou H, Zhang Y, Shen Z, Guo H, Zhang Y, Rui K, Xu H, Wang S.
Preprint from
Research Square
7 August 2020
PPR
PPR198186
Abstract

Background:

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltrates in exocrine glands. Mesenchymal stem cells (MSCs) have been proved to be effective in the treatment of different autoimmune diseases. Although MSC transplantation has been demonstrated to be an effective therapeutic approach to treat SS, the underlying mechanisms are still elusive. Our previous study has identified the reduced suppressive capacity of MDSCs advanced the progression of experimental Sjögren’s syndrome (ESS). Methods The ESS mouse model was induced with murine salivary glands proteins emulsified in an equal volume of Freund’s adjuvant. Both frequency and phenotype of MDSCs during ESS development in mice were analyzed by flow cytometry. The suppressive capacity of MDSCs was examined by CD4 + T cell proliferation test, CFSE-labelled CD4 + T cell was analyzed by flow cytometry. Both phenotype and function of MDSCs upon MSCs treatment were analyzed in vitro and in vivo . The function of MSCs in modulating the suppressive function of MDSCs was further evaluated by silencing TGF-β in MSCs. Results In this study, we found that BM-MSCs significantly enhanced the suppressive function of MDSCs (PMN-MDSCs/M-MDSCs) with high levels of Arginase and NO, decreased the levels of CD40, CD80, CD86 and MHC-II expression on MDSCs, thus attenuating the disease progression in ESS mice. Furthermore, the enhanced suppressive function of MDSCs was mediated by BM-MSC-secreted TGF-β, and the therapeutic effect of BM-MSCs in inhibiting ESS was almost abolished after silencing TGF-β in BM-MSCs. Conclusions Taken together, our results demonstrated that BM-MSCs alleviated the ESS progression by up-regulating the immunosuppressive effect of MDSCs through TGF-β/Smad pathway, offering a novel mechanism for MSCs in the treatment of pSS.