Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production

Ting Feng, Hongwei Qin, Lanfang Wang, Etty N. Benveniste, Charles O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Both Th1 and Th17 cells have been implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. However, the complex relationship between Th1 and Th17 cells and their relative contributions to the pathogenesis of inflammatory bowel disease have not been completely analyzed. Although it has been recently shown that Th17 cells can convert into Th1 cells, the underlying in vivo mechanisms and the role of Th1 cells converted from Th17 cells in the pathogenesis of colitis are still largely unknown. In this study, we report that Th17 cells from CBir1 TCR transgenic mice, which are specific for an immunodominant microbiota Ag, are more potent than Th1 cells in the induction of colitis, as Th17 cells induced severe colitis, whereas Th1 cells induced mild colitis when transferred into TCRβxδ-/- mice. High levels of IL-12 and IL-23 and substantial numbers of IFN- γ+ Th1 cells emerged in the colons of Th17 cell recipients. Administration of anti - IL-17 mAb abrogated Th17 cell-induced colitis development, blocked colonic IL-12 and IL-23 production, and inhibited IFN-γ+ Th1 cell induction. IL-17 promoted dendritic cell production of IL-12 and IL-23. Furthermore, conditioned media from colonic tissues of colitic Th17 cell recipients induced IFN-γ production by Th17 cells, which was inhibited by blockade of IL-12 and IL-23. Collectively, these data indicate that Th17 cells convert to Th1 cells through IL-17 induction of mucosal innate IL-12 and IL-23 production.

Original languageEnglish (US)
Pages (from-to)6313-6318
Number of pages6
JournalJournal of Immunology
Volume186
Issue number11
DOIs
StatePublished - Jun 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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