IL-17 down-regulates the immunosuppressive capacity of olfactory ecto-mesenchymal stem cells in murine collagen-induced arthritis.

Jie Tian,Xinyi Tang,Wenxin Wang,Huaxi Xu,Yungang Wang,Ke Rui,Xinyu Tian,Jie Ma,Shengjun Wang,Liwei Lu

doi:10.18632/oncotarget.10261

Abstract

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a new resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses, including up-regulation of regulatory T cells (Tregs) and down-regulation of Th1/Th17 cells. As an inflammatory cytokine, IL-17 plays a critical role in orchestrating the inflammatory response during the development of collagen-induced arthritis (CIA). However, it is unclear whether the increased level of IL-17 may affect the immunosuppressive function of OE-MSCs under inflammatory condition. In this study, we found that IL-17 could significantly reduce the suppressive capacity of OE-MSCs on CD4+ T cells and down-regulate the suppressive factors produced by OE-MSCs. Notably, IL-17 treatment abolished the capacity of OE-MSCs in inducing Treg expansion. In addition, knockdown of IL-17R in OE-MSCs significantly enhanced their therapeutic effect in ameliorating CIA upon adoptive transfer. Moreover, IL-17R knockdown-OE-MSCs could efficiently induce Tregs expansion and reduce Th1 and Th17 responses. Taken together, all these data suggest that IL-17R knockdown in OE-MSCs may provide a novel strategy in maintaining their immunosuppressive properties for the treatment of autoimmune diseases.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease caused by chronic joint inflammation, leading to cartilage destruction and bone erosion [1]
In an effort to determine if IL-17 treatment has any effect on the suppressive function of olfactory ecto-mesenchymal stem cells (OE-Mesenchymal stem cells (MSCs)) in vitro, we co-cultured CD4+ T cells with OEMSCs treated with or without IL-17
It is reported that MSCs could induce the generation of Tregs from CD4+ or CD8+ T cells, and these Tregs have powerful immunosuppression that strongly inhibit lymphocytes [21, 22]

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease caused by chronic joint inflammation, leading to cartilage destruction and bone erosion [1]. MSCs have been considered to have potent immunosuppressive and anti-inflammatory effects via cell-cell contact or by secreting soluble factors, such as IL-10, NO, TGF-β, indoleamine 2, 3-dioxygenase (IDO), prostaglandin E2 (PGE2) and so on [8, 9]. They effectively impair the proliferation or the activation of T cells, B cells, NK cells and antigen presenting cells, raising great interest for their potential therapeutic application. The MSC-based immunotherapy has shown significant effect in CIA treatment, the application of MSCs in clinic still encounters different difficulties, such as some patients with autoimmune diseases are not sensitive to the MSCs treatment

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Results

Conclusion