title: A subset of IL-17(+) mesenchymal stem cells possesses anti-Candida albicans effect.
abstract: 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.
authors.affiliation: Department of Orthodontics, Peking University, School & Hospital of Stomatology, #22 Zhongguancun South Avenue, Beijing 100081, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Peyman
authors.initials: P
authors.lastname: Kelk
authors.forename: Cunye
authors.initials: C
authors.lastname: Qu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akiyama
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.forename: Ikiru
authors.initials: I
authors.lastname: Atsuta
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002177:Candidiasis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta