J Cell Mol Med. 2016 Mar 29. doi: 10.1111/jcmm.12849. [Epub ahead of print]

A20 plays a critical role in the immunoregulatory function of mesenchymal stem cells.

Dang RJ^1,2, Yang YM^1,2, Zhang L^2,3, Cui DC⁴, Hong B⁵, Li P^1,2, Lin Q², Wang Y², Wang QY², Xiao F⁶, Mao N², Wang C², Jiang XX², Wen N¹.

Abstract

Mesenchymal stem cells (MSCs) possess an immunoregulatory capacity and are a therapeutic target for many inflammation-related diseases. However, the detailed mechanisms of MSC-mediated immunosuppression remain unclear. In this study, we provide new information to partly explain the molecular mechanisms of immunoregulation by MSCs. Specifically, we found that A20 expression was induced in MSCs by inflammatory cytokines. Knockdown of A20 in MSCs resulted in increased proliferation and reduced adipogenesis, and partly reversed the suppressive effect of MSCs on T cell proliferation in vitro and inhibited tumour growth in vivo. Mechanistic studies indicated that knockdown of A20 in MSCs inhibited activation of the p38 mitogen-activated protein kinase (MAPK) pathway, which potently promoted the production of tumour necrosis factor (TNF)-α and inhibited the production of interleukin (IL)-10. Collectively, these data reveal a crucial role of A20 in regulating the immunomodulatory activities of MSCs by controlling the expression of TNF-α and IL-10 in an inflammatory environment. These findings provide novel insights into the pathogenesis of various inflammatory-associated diseases, and are a new reference for the future development of treatments for such afflictions.