Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis

Keiichiro Saigusa, Tadakazu Hisamatsu, Tango Handa, Tomohisa Sujino, Yohei Mikami, Atsushi Hayashi, Shinta Mizuno, Kozue Takeshita, Toshiro Sato, Katsuyoshi Matsuoka, Takanori Kanai

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Background: Both Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood. Methods: We performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhigh T cells obtained from wild-type, RORγtgfp/gfp, or RORγtgfp/+ mice into RAG-2-/- mice. Results: RAG-2-/- mice receiving transfer of in vitro-manipulated RORγtgfp/gfp Th1 cells developed colitis. RAG-2-/- mice co-transferred with splenic CD4+CD45RBhigh T cells obtained from wild-type mice and RORγtgfp/gfp mice developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RBhigh T cells obtained from RORγtgfp/gfp mice. Furthermore, RAG-2-/- mice transferred with in vivo-manipulated RORγtgfp/gfp cTh1 cells developed colitis with a significant increase in RORγtgfp/gfp cTh1 cell numbers. Conclusions: These findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.

本文言語English
ページ(範囲)1820-1827
ページ数8
ジャーナルInflammatory bowel diseases
20
10
DOI
出版ステータスPublished - 2014 10 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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