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

Ruili Yang, Yi Liu, Peyman Kelk, Cunye Qu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta, Wanjun Chen, Yanheng Zhou, Songtao Shi

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37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)107-121
Number of pages15
JournalCell Research
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

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Keywords

  • Development
  • Immunity
  • Molecular pathogenesis
  • Stem cell biology

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Yang, R., Liu, Y., Kelk, P., Qu, C., Akiyama, K., Chen, C., Atsuta, I., Chen, W., Zhou, Y., & Shi, S. (2013). A subset of IL-17 + mesenchymal stem cells possesses anti-Candida albicans effect. Cell Research, 23(1), 107-121. https://doi.org/10.1038/cr.2012.179