A subset of IL-17(+) mesenchymal stem cells possesses anti-Candida albicans effect

Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties, such as upregulation of Foxp3(+) regulatory T cells (Tregs) and downregulation of Th17 cells. However, it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function. Here, we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs, downregulate Th17 cells, or ameliorate disease phenotypes in a colitis mouse model. Mechanistically, we reveal that IL-17, produced by these MSCs, activates the NF kappa B pathway to downregulate TGF-beta production in MSCs, resulting in abolishment of MSC-based immunomodulation. Furthermore, we show that NF kappa B is able to directly bind to TGF-beta promoter region to regulate TGF-beta expression in MSCs. Moreover, these IL-17(+) MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C. albicans-infected mice. In summary, this study shows that MSCs contain an IL-17(+) subset capable of inhibiting C. albicans growth, but attenuating MSC-based immunosuppression via NF kappa B-mediated downregulation of TGF-beta.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000313194700014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell BiologySCI(E)PubMed中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)19ARTICLE1,SI107-1212