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Volume 23, No 1, Jan 2013
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 23 Issue 1, January 2013: 107-121
Ruili Yang1,2,*, Yi Liu2,*, Peyman Kelk2, Cunye Qu2, Kentaro Akiyama2, Chider Chen2, Ikiru Atsuta2, WanJun Chen3, Yanheng Zhou1 and Songtao Shi2
1Department of Orthodontics, Peking University, School & Hospital of Stomatology, #22 Zhongguancun South Avenue, Beijing 100081, China
2Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA
3National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-2190, USA
Correspondence: Songtao Shi,Yanheng Zhou,(songtaos@usc.edu;yanhengzhou@gmail.com)
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.
Cell Research (2013) 23:107-121. doi:10.1038/cr.2012.179; published online 25 December 2012
