Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis

Motomi Yamazaki, Tomoharu Yajima, Masanobu Tanabe, Kazuto Fukui, Eriko Okada, Ryuichi Okamoto, Shigeru Oshima, Tetsuya Nakamura, Takanori Kanai, Masahiro Uehira, Tsutomu Takeuchi, Hiromichi Ishikawa, Toshifumi Hibi, Mamoru Watanabe

Research output: Contribution to journalArticle

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Abstract

The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR α-chain knockout mice and IL-7 transgenic mice. Transfer of mucosai T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2-/- mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.

Original languageEnglish
Pages (from-to)1556-1563
Number of pages8
JournalJournal of Immunology
Volume171
Issue number3
Publication statusPublished - 2003 Aug 1
Externally publishedYes

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Interleukin-7 Receptors
Colitis
T-Lymphocytes
Interleukin-7
Recombinases
Intestinal Mucosa
Inflammatory Bowel Diseases
Knockout Mice
Transgenic Mice
Mucous Membrane
Inflammation
Therapeutics
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Yamazaki, M., Yajima, T., Tanabe, M., Fukui, K., Okada, E., Okamoto, R., ... Watanabe, M. (2003). Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. Journal of Immunology, 171(3), 1556-1563.

Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. / Yamazaki, Motomi; Yajima, Tomoharu; Tanabe, Masanobu; Fukui, Kazuto; Okada, Eriko; Okamoto, Ryuichi; Oshima, Shigeru; Nakamura, Tetsuya; Kanai, Takanori; Uehira, Masahiro; Takeuchi, Tsutomu; Ishikawa, Hiromichi; Hibi, Toshifumi; Watanabe, Mamoru.

In: Journal of Immunology, Vol. 171, No. 3, 01.08.2003, p. 1556-1563.

Research output: Contribution to journalArticle

Yamazaki, M, Yajima, T, Tanabe, M, Fukui, K, Okada, E, Okamoto, R, Oshima, S, Nakamura, T, Kanai, T, Uehira, M, Takeuchi, T, Ishikawa, H, Hibi, T & Watanabe, M 2003, 'Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis', Journal of Immunology, vol. 171, no. 3, pp. 1556-1563.
Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R et al. Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. Journal of Immunology. 2003 Aug 1;171(3):1556-1563.
Yamazaki, Motomi ; Yajima, Tomoharu ; Tanabe, Masanobu ; Fukui, Kazuto ; Okada, Eriko ; Okamoto, Ryuichi ; Oshima, Shigeru ; Nakamura, Tetsuya ; Kanai, Takanori ; Uehira, Masahiro ; Takeuchi, Tsutomu ; Ishikawa, Hiromichi ; Hibi, Toshifumi ; Watanabe, Mamoru. / Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. In: Journal of Immunology. 2003 ; Vol. 171, No. 3. pp. 1556-1563.
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