Depletion of androgen receptor (AR) in mesenchymal stem cells (MSCs) inhibits induction of CD4+CD25+FOX3+regulatory T (Treg) cells via androgen TGF-β interaction

MSCs produce CD4(+)CD25(+)FOX3(+) regulatory T(Treg) cells from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and T-CD8+ cells in vitro and in vivo. Here we investigated whether the deficiency of androgen/AR in MSCs influence Treg induction from total PBMC, splenocytes, CD4+CD25-through AR/TGF-beta interaction. Eight to 12-week-old wild type and general androgen receptor knockout (ARKO) mice were used. MSCs were collected, characterized and function of Treg cells was studied. Our result showed that depletion of AR suppressed the immunosuppressive effect of MSCs, and demonstrated that WT-MSC-induced Treg cell expansion was partially impaired by blocking androgen receptor signal. Furthermore, the levels of TGF-beta were lower in the T cell coculture with ARKO-MSC compared to WT-MSC. Exposure of ARKO-MSC cells to exogenous active TGF-beta partially restored the induction of Treg cell expansion by ARKO-MSC cells. Our data suggest that ARKO-MSC hampers Treg cell expansion and function via androgen/AR and TGF-beta signal pathways interaction. To the best of our knowledge, this study is the first investigating the interaction of MSCs from ARKO mice and WT Tregs in an allogeneic co-culture model. Together, these results might provide great insight into treatment of inflammatory and autoimmune diseases. (C) 2015 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Sp. z o.o. All rights reserved.