TY - JOUR
T1 - A subset of IL-17 + mesenchymal stem cells possesses anti-Candida albicans effect
AU - Yang, Ruili
AU - Liu, Yi
AU - Kelk, Peyman
AU - Qu, Cunye
AU - Akiyama, Kentaro
AU - Chen, Chider
AU - Atsuta, Ikiru
AU - Chen, Wanjun
AU - Zhou, Yanheng
AU - Shi, Songtao
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
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U2 - 10.1038/cr.2012.179
DO - 10.1038/cr.2012.179
M3 - Article
C2 - 23266891
AN - SCOPUS:84872037312
VL - 23
SP - 107
EP - 121
JO - Cell Research
JF - Cell Research
SN - 1001-0602
IS - 1
ER -