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, Atsuta Ikiru, Wanjun Chen, Yanheng Zhou, Songtao Shi

Research output: Contribution to journalArticle

33 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 1 2013
Externally publishedYes

Fingerprint

Interleukin-17
Candida albicans
Mesenchymal Stromal Cells
Down-Regulation
Th17 Cells
Up-Regulation
Immunomodulation
Therapeutic Uses
Regulatory T-Lymphocytes
Colitis
Growth
Genetic Promoter Regions
Immunosuppression
Population
Stem Cells
Bone Marrow
Phenotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Yang, R., Liu, Y., Kelk, P., Qu, C., Akiyama, K., Chen, C., ... 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

A subset of IL-17 + mesenchymal stem cells possesses anti-Candida albicans effect. / Yang, Ruili; Liu, Yi; Kelk, Peyman; Qu, Cunye; Akiyama, Kentaro; Chen, Chider; Ikiru, Atsuta; Chen, Wanjun; Zhou, Yanheng; Shi, Songtao.

In: Cell Research, Vol. 23, No. 1, 01.01.2013, p. 107-121.

Research output: Contribution to journalArticle

Yang, R, Liu, Y, Kelk, P, Qu, C, Akiyama, K, Chen, C, Ikiru, A, Chen, W, Zhou, Y & Shi, S 2013, 'A subset of IL-17 + mesenchymal stem cells possesses anti-Candida albicans effect', Cell Research, vol. 23, no. 1, pp. 107-121. https://doi.org/10.1038/cr.2012.179
Yang, Ruili ; Liu, Yi ; Kelk, Peyman ; Qu, Cunye ; Akiyama, Kentaro ; Chen, Chider ; Ikiru, Atsuta ; Chen, Wanjun ; Zhou, Yanheng ; Shi, Songtao. / A subset of IL-17 + mesenchymal stem cells possesses anti-Candida albicans effect. In: Cell Research. 2013 ; Vol. 23, No. 1. pp. 107-121.
@article{b358d82cc68c447bb3549fac8a3f7dbe,
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.",
author = "Ruili Yang and Yi Liu and Peyman Kelk and Cunye Qu and Kentaro Akiyama and Chider Chen and Atsuta Ikiru and Wanjun Chen and Yanheng Zhou and Songtao Shi",
year = "2013",
month = "1",
day = "1",
doi = "10.1038/cr.2012.179",
language = "English",
volume = "23",
pages = "107--121",
journal = "Cell Research",
issn = "1001-0602",
publisher = "Nature Publishing Group",
number = "1",

}

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 - Ikiru, Atsuta

AU - Chen, Wanjun

AU - Zhou, Yanheng

AU - Shi, Songtao

PY - 2013/1/1

Y1 - 2013/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84872037312&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872037312&partnerID=8YFLogxK

U2 - 10.1038/cr.2012.179

DO - 10.1038/cr.2012.179

M3 - Article

VL - 23

SP - 107

EP - 121

JO - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 1

ER -