Olfactory ecto-mesenchymal stem cells derived exosomes reverse the immunosuppressive capacity of myeloid-derived suppressor cells to ameliorates experimental Sjögren’s syndrome

Abstract

Abstract Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage of salivary glands and lacrimal glands. Our previous studies have shown myeloid-derived suppressor cells (MDSCs) were significantly increased but exhibited gradually diminished suppressive capacity in experimental Sjögren’s syndrome (ESS), thus leading to the development of the disease. In this study, we found that exosomes derived from olfactory ecto-mesenchymal stem cells (OE-MSCs-Exo) effectively enhanced the suppressive function of MDSCs on T cell proliferation, up-regulated MDSC-mediated suppressive factors (Arginase, ROS and NO), and subsequently suppressing the development of ESS. Additionally, levels of CD40, CD80, CD86 and MHCII on MDSCs were dramatically decreased, indicating the differentiated late stage MDSCs were reversed to the original undifferentiated status by OE-MSCs-Exo. Further investigation demonstrated that the increased suppressive function of MDSCs was orchestrated by IL-6, from both exosomes secreted IL-6 as well as its own IL-6 autocrine signaling pathway. Taken together, OE-MSCs-Exo have the potential to alleviate ESS severity through inducing MDSC expansion and potentiating their immunosuppressive function, indicating OE-MSCs-Exo may represent a new therapeutic strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.