IL-7 exacerbates chronic colitis with expansion of memory IL-7R high CD4+ mucosal T cells in mice

Eriko Okada, Motomi Yamazaki, Masanobu Tanabe, Tsutomu Takeuchi, Masanobu Nanno, Shigeru Oshima, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Takanori Kanai, Toshifumi Hibi, Mamoru Watanabe

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35 Citations (Scopus)

Abstract

We have previously demonstrated that mucosal CD4+ T cells expressing high levels of IL-7 receptor (IL-7Rhigh) are pathogenic cells responsible for chronic colitis. Here we investigate whether IL-7 is directly involved in the expansion of IL-7Rhigh memory CD4 + mucosal T cells and the exacerbation of colitis. We first showed that CD4+ lamina propria lymphocytes (LPLs) from wild-type, T cell receptor-α-deficient (TCR-α-/-), and recombinase- activating gene (RAG)-2-/--transferred mice with or without colitis showed phenotypes of memory cells, but only CD4+ LPLs from colitic mice showed IL-7Rhigh. In vitro stimulation by IL-7, but not by IL-15 and thymic stromal lymphopoietin, enhanced significant proliferative responses and survival of colitic CD4+, but not normal CD4+ LPLs. Importantly, in vivo administration of IL-7 mice accelerated the expansion of IL-7Rhigh memory CD4+ LPLs and thereby exacerbated chronic colitis in RAG-2-/- mice transferred with CD4+ LPLs from colitic TCR-α-/- mice. Conversely, the administration of anti-IL-7R monoclonal antibody significantly inhibited the development of TCR-α-/- colitis with decreased expansion of CD4+ LPLs. Collectively, the present data indicate that IL-7 is essential for the expansion of pathogenic memory CD4+ T cells under pathological conditions. Therefore, therapeutic approaches targeting the IL-7R pathway may be feasible in the treatment of human inflammatory bowel disease.

Original languageEnglish
Pages (from-to)G745-G754
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number4 51-4
DOIs
Publication statusPublished - 2005 Apr

Keywords

  • Colitis
  • High-level interleukin-7 receptor
  • Interleukin-7
  • Lamina propria lymphocytes
  • Memory T cells
  • Proliferation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Okada, E., Yamazaki, M., Tanabe, M., Takeuchi, T., Nanno, M., Oshima, S., Okamoto, R., Tsuchiya, K., Nakamura, T., Kanai, T., Hibi, T., & Watanabe, M. (2005). IL-7 exacerbates chronic colitis with expansion of memory IL-7R high CD4+ mucosal T cells in mice. American Journal of Physiology - Gastrointestinal and Liver Physiology, 288(4 51-4), G745-G754. https://doi.org/10.1152/ajpgi.00276.2004