Mesenchymal Stem Cell Enhances the Function of MDSCs in Experimental Sjögren Syndrome

Jie Tian,Hongye Guo,Shengjun Wang,Huaxi Xu,Huimin Zhou,Qiugang Zhu,Yue Hong,Futao Zhao,Yue Zhang,Ke Rui,Xiangyan Ai,Ziwei Shen,Yidan Zhang

doi:10.3389/fimmu.2020.604607

Abstract

Primary Sjögren’s syndrome (pSS) is a progressive systemic autoimmune disease characterized by lymphocytic infiltrates in exocrine glands, leading to the injury of salivary and lachrymal glands. Mesenchymal stem cells (MSCs) have been demonstrated to exert great potential in the treatment of various autoimmune diseases. Although MSCs have provide an effective therapeutic approach for SS treatment, the underlying mechanisms are still elusive. Our previous study has shown the reduced suppressive capacity of myeloid-derived suppressor cells (MDSCs) advanced the progression of experimental Sjögren’s syndrome (ESS). In this study, we found that BM-MSCs significantly enhanced the suppressive function of 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. 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.

Highlights

Primary Sjögren’s syndrome is a chronic, systemic autoimmune disease characterized by lymphocytic infiltrates in salivary and lacrimal glands, leading to the destruction of these exocrine glands
We found that myeloid-derived suppressor cells (MDSCs) were significantly increased in mice with experimental Sjögren’s syndrome (ESS), but their suppressive function of MDSCs was gradually decreased with the progression of the disease, and eventually leading to the uncontrollable inflammatory responses and irreversible tissue injury
Some other studies have shown that MDSCs in EAE could promote the differentiation of Th17 cells, and the severity of disease can be alleviated after depletion of MDSCs in vivo [15]

Summary

Introduction

Primary Sjögren’s syndrome (pSS) is a chronic, systemic autoimmune disease characterized by lymphocytic infiltrates in salivary and lacrimal glands, leading to the destruction of these exocrine glands. Besides the characteristic glandular symptoms, other systemic extraglandular manifestations, including synovitis, interstitial lung disease, vasculitis and renal diseases [2]. Approximately 5% of patients with pSS may BM-MSCs Regulate MDSCs in ESS develop lymphoma, mainly the mucosa-associated lymphoid tissue non-Hodgkin lymphoma, which is the most severe complication of the disease [3]. Treatment of Sjögren’s syndrome patients is still challenging due to the complex pathogenesis of the disease, approaches such as biologic agents and traditional diseasemodifying antirheumatic drugs cannot cure this disease and have some side effects [8]. Exploring novel therapeutic approaches is critically necessary for the treatment of pSS

Methods

Results

Conclusion