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

摘要

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 NFκB pathway to downregulate TGF-β production in MSCs,resulting in abolishment of MSC-based immunomodulation.Furthermore,we show that NFκB is able to directly bind to TGF-β promoter region to regulate TGF-β 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 NFκB-mediated downregulation of TGF-β.