TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression

Hou Pu Liu, Anthony T. Cao, Ting Feng, Qingjie Li, Wenbo Zhang, Suxia Yao, Sara Dann-Grice, Charles O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Differentiated CD4<sup>+</sup> T cells preserve plasticity under various conditions. However, the stability of Th1 cells is unclear, as is whether Th1 cells can convert into Th17 cells and thereby contribute to the generation of IFN-γ<sup>+</sup>IL-17<sup>+</sup>CD4<sup>+</sup> T cells, the number of which correlates with severity of colitis. We investigated whether IFN-γ<sup>+</sup>Th1 cells can convert into Th17 cells under intestinal inflammation and the mechanisms involved. IFN-γ<sup>Thy1.1+</sup> Th1 cells were generated by culturing naïve CD4<sup>+</sup> T cells from IFN-γ<sup>Thy1.1</sup> CBir1 TCR-Tg reporter mice, whose TCR is specific for an immunodominant microbiota antigen, CBir1 flagellin, under Th1 polarizing conditions. IFN-γ<sup>Thy1.1+</sup> Th1 cells induced colitis in Rag<sup>-/-</sup> mice after adoptive transfer and converted into IL-17<sup>+</sup>Th17, but not Foxp3<sup>+</sup>Treg cells in the inflamed intestines. TGF-β and IL-6, but not IL-1β and IL-23, regulated Th1 conversion into Th17 cells. TGF-β induction of transcriptional factor Runx1 is crucial for the conversion, since silencing Runx1 by siRNA inhibited Th1 conversion into Th17 cells. Furthermore, TGF-β enhanced histone H3K9 acetylation but inhibited H3K9 trimethylation of Runx1- and ROR-γt-binding sites on il-17 or rorc gene in Th1 cells. We conclude that Th1 cells convert into Th17 cells under inflammatory conditions in intestines, which is possibly mediated by TGF-β induction of Runx1.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalEuropean Journal of Immunology
Volume45
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Th17 Cells
Th1 Cells
Interleukin-17
Colitis
T-Lymphocytes
Intestines
Interleukin-23
Immunodominant Epitopes
Adoptive Transfer
Microbiota
Regulatory T-Lymphocytes
Acetylation
Interleukin-1
Histones
Small Interfering RNA
Interleukin-6
Cell Count
Binding Sites
Inflammation
Genes

Keywords

  • Colitis
  • Runx1
  • TGF-β
  • Th1
  • Th17

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression. / Liu, Hou Pu; Cao, Anthony T.; Feng, Ting; Li, Qingjie; Zhang, Wenbo; Yao, Suxia; Dann-Grice, Sara; Elson, Charles O.; Cong, Yingzi.

In: European Journal of Immunology, Vol. 45, No. 4, 01.04.2015, p. 1010-1018.

Research output: Contribution to journalArticle

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AU - Cao, Anthony T.

AU - Feng, Ting

AU - Li, Qingjie

AU - Zhang, Wenbo

AU - Yao, Suxia

AU - Dann-Grice, Sara

AU - Elson, Charles O.

AU - Cong, Yingzi

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