Digestive Diseases and Sciences

, Volume 56, Issue 2, pp 376–386

CD4+CD25+ Regulatory T Cells Suppress Th17-Responses in an Experimental Colitis Model

  • Haruei Ogino
  • Kazuhiko Nakamura
  • Eikich Ihara
  • Hirotada Akiho
  • Ryoichi Takayanagi
Original Article
  • 435 Downloads

Abstract

Background

After the recent discovery of Th17 cells, it was proposed that Th17 responses are involved in the pathogenesis of inflammatory bowel diseases (IBD). CD4+CD25+ regulatory T cells (Treg) are considered to be an attractive tool for the treatment of IBD. Here, we investigated whether Treg are capable of suppressing Th17-mediated colitis.

Methods

Naive CD4+ T cells were transferred into SCID mice with or without Treg. In some experiments, Treg were transferred into recipient mice with established colitis. Mice treated with Treg were injected with an anti-transforming growth factor (TGF)-β mAb or control IgG. Clinical symptoms of colitis, histological changes and cytokine expressions were investigated.

Results

SCID mice transferred with naive CD4+ T cells developed chronic colitis with significant increases in Th1 and Th17 cytokine expressions in the colon. When Treg were co-transferred with naive CD4+ T cells, development of colitis was prevented, and Th17 cytokine expressions were markedly reduced. Similarly, when Treg were transferred into mice with established colitis, the colitis was significantly ameliorated in association with dramatic reductions in Th17 cytokine expressions. Injection of anti-TGF-β mAb abolished the Treg-mediated suppression with significant elevations in Th17 cytokine productions.

Conclusion

This adoptive transfer model of colitis was associated with augmented Th1 and Th17 responses, and Treg were capable of suppressing colonic inflammation by downregulating Th17 responses as well as Th1 responses via TGF-β. Consequently, Treg transfer therapy is expected to be efficacious for IBD even if Th17 is involved in the pathogenesis.

Keywords

Colitis model Inflammatory bowel diseases Regulatory T cells T helper 17 cells Transforming growth factor-β 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Haruei Ogino
    • 1
  • Kazuhiko Nakamura
    • 1
  • Eikich Ihara
    • 1
  • Hirotada Akiho
    • 1
  • Ryoichi Takayanagi
    • 1
  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical SciencesKyushu UniversityHigashi-ku, FukuokaJapan

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