Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice

Min-Jung Park,Eun-Jung Lee,Eun-Kyung Kim,Sung-Hwan Park,Mi-La Cho,Sung-Hee Lee,Jin-Ah Baek,Seung-Ki Kwok

doi:10.1038/s41598-018-21856-2

Min-Jung Park, Eun-Jung Lee + Show 6 more

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https://doi.org/10.1038/s41598-018-21856-2

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Abstract

Myeloid-derived suppressor cells (MDSCs) are heterogenous populations of immature myeloid progenitor cells with immunoregulatory function. MDSCs play critical roles in controlling the processes of autoimmunity but their roles in rheumatoid arthritis (RA) are controversial. The present study was undertaken to investigate whether MDSCs have therapeutic impact in mice with collagen-induced arthritis (CIA), an animal model of RA. We also examined the mechanisms underlying the anti-arthritic effect of MDSCs. In vitro treatment with MDSCs repressed IL-17 but increased FOXP3 in CD4+ T cells in mice. In vivo infusion of MDSCs markedly ameliorated inflammatory arthritis. Th17 cells and Th1 cells were decreased while Tregs were increased in the spleens of MDSCs-treated mice. MDSCs profoundly inhibited T cell proliferation. Addition of anti-IL-10 almost completely blocked the anti-proliferative effects of MDSCs on T cells. Anti-IL-10 blocked the expansion of Tregs by MDSCs. However, infusion of MDSCs from IL-10 KO mice failed to suppress inflammatory arthritis. MDSCs could reciprocally regulate Th17/Treg cells and suppress CIA via IL-10, suggesting that MDSCs might be a promising therapeutic strategy for T cell mediated autoimmune diseases including RA.

Highlights

Myeloid-derived suppressor cells (MDSCs) are a heterogenous group of immune cells from the myeloid lineage
The results showed the addition of MDSCs obtained from collagen-induced arthritis (CIA) mice profoundly decreased T cell proliferative response to CII whereas the addition of monocytes failed to show any impact (Fig. 2E)
The mechanisms of MDSC-induced immune suppression have been widely studied. It is well-known that the main immunoregulatory activity of MDSCs is associated with the production of arginase-1, inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), which can induce the inactivation of various immune cells, especially T cells[1]

Summary

Introduction

Myeloid-derived suppressor cells (MDSCs) are a heterogenous group of immune cells from the myeloid lineage. MDSCs strongly expanded under pathologic conditions including the tumor environment and chronic inflammation. They play a pivotal role owing to their potent suppressive activities in immune response[1,2]. These cells produce immunoregulatory mediators including arginase-1, inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), which can inhibit the activation of various immune cells, especially T cells[3]. Murine MDSCs can be characterized by the expression of CD11b and Gr-1. Considering the potent immunoregulatory effect of MDSCs on T cells, it can be spec ulated that MDSCs might have therapeutic effect on RA. The precise impact of MDSCs on RA remains still unclear

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