Exacerbating Role of γδ T Cells in Chronic Colitis of T-Cell Receptor α Mutant Mice

Masanobu Nanno, Yasuyoshi Kanari, Tomoaki Naito, Nagamu Inoue, Tadakazu Hisamatsu, Hiroshi Chinen, Ken Sugimoto, Yasuyo Shimomura, Hideo Yamagishi, Tetsuo Shiohara, Satoshi Ueha, Kouji Matsushima, Makoto Suematsu, Atsushi Mizoguchi, Toshifumi Hibi, Atul K. Bhan, Hiromichi Ishikawa

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Abstract

Background & Aims: T-cell receptor (TCR) γδ T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in γδ T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of γδ T cells in chronic colitis has not been fully identified. Methods: TCRα-deficient mice, which spontaneously develop chronic colitis with many features of human UC including an increase in γδ T-cell population, represent an excellent model to investigate the role of γδ T cells in UC-like colitis. To identify the role of γδ T cells in this colitis, we herein have generated TCRγ-deficient mice through deletion of all TCR Cγ genes (Cγ1, Cγ2, Cγ3, and Cγ4) using the Cre/loxP site-specific recombination system and subsequently crossing these mice with TCRα-deficient mice. Results: An increase in colonic γδ T cells was associated with the development of human UC as well as UC-like disease seen in TCRα-deficient mice. Interestingly, the newly established TCRα-/- × TCRγ-/- double mutant mice developed significantly less severe colitis as compared with TCRα-deficient mice. The suppression of colitis in TCRα-/- × TCRγ-/- double mutant mice was associated with a significant reduction of proinflammatory cytokine and chemokine productions and a decrease in neutrophil infiltration. Conclusions: γδ T cells are involved in the exacerbation of UC-like chronic disease. Therefore, γδ T cells may represent a promising therapeutic target for the treatment of human UC.

Original languageEnglish
Pages (from-to)481-490
Number of pages10
JournalGastroenterology
Volume134
Issue number2
DOIs
Publication statusPublished - 02-2008

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All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Nanno, M., Kanari, Y., Naito, T., Inoue, N., Hisamatsu, T., Chinen, H., Sugimoto, K., Shimomura, Y., Yamagishi, H., Shiohara, T., Ueha, S., Matsushima, K., Suematsu, M., Mizoguchi, A., Hibi, T., Bhan, A. K., & Ishikawa, H. (2008). Exacerbating Role of γδ T Cells in Chronic Colitis of T-Cell Receptor α Mutant Mice. Gastroenterology, 134(2), 481-490. https://doi.org/10.1053/j.gastro.2007.11.056