Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis

Yohei Mikami, Takanori Kanai, Tomohisa Sujino, Yuichi Ono, Atsushi Hayashi, Akira Okazawa, Nobuhiko Kamada, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Susumu Okamoto, Hiromasa Takaishi, Nagamu Inoue, Haruhiko Ogata, Toshifumi Hibi

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Th17 cells and Th1 cells coordinate to play a critical role in the formation of inflammatory bowel diseases. To examine how Th17 and Th1 cells are regulated at inflammatory sites, we used Th1-dominant CD4+CD45RB high T cell-transferred RAG-2-/- and Th1/Th17-mixed IL-10-/- mice. Interestingly, not only did colitic RAG-2 -/- mice that were parabiosed with WT mice show significant amelioration of colitis, but amelioration of disease was also observed in those parabiosed with colitic IL-10-/- mice. To assess the interference between Th1 and Th17 colitogenic T cells, we co-transferred colitogenic CD4 + T cells from the lamina propria (LP) of CD4+CD45RB high T cell-transferred RAG-2-/- mice and IL-10 -/- mice into RAG-2-/- mice. Surprisingly, the co-transferred RAG-2-/- mice showed a vast cellular infiltration of LP CD4+ T cells similar to that seen in RAG-2-/- mice re-transferred with the cells from colitic RAG-2-/- mice alone, but the co-transferred RAG-2-/- mice did not have the wasting symptoms, which are also absent in RAG-2-/- mice transferred with cells from colitic IL-10-/- mice alone. Furthermore, the percentages of Th1 and Th17 cells originating from IL-10-/- mice and those of Th1 cells originating from colitic RAG-2-/- mice were all significantly decreased in the co-transferred mice as compared with the singly-transferred paired RAG-2-/- mice, suggesting that Th1 and Th17 cells are in competition, and that their orchestration results in a merged clinical phenotype of the two types of murine colitis.

Original languageEnglish
Pages (from-to)2409-2422
Number of pages14
JournalEuropean Journal of Immunology
Volume40
Issue number9
DOIs
Publication statusPublished - 2010 Sep

Keywords

  • Cytokines
  • Inflammation
  • Mucosa
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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