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

Research output: Contribution to journalArticle

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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
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number4 51-4
DOIs
Publication statusPublished - 2005 Apr
Externally publishedYes

Fingerprint

Interleukin-7
Colitis
Mucous Membrane
Lymphocytes
T-Lymphocytes
T-Cell Antigen Receptor
Recombinases
Interleukin-7 Receptors
Interleukin-15
Inflammatory Bowel Diseases
Genes
Monoclonal Antibodies
Phenotype
Survival

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

IL-7 exacerbates chronic colitis with expansion of memory IL-7R high CD4+ mucosal T cells in mice. / Okada, Eriko; Yamazaki, Motomi; Tanabe, Masanobu; Takeuchi, Tsutomu; Nanno, Masanobu; Oshima, Shigeru; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Kanai, Takanori; Hibi, Toshifumi; Watanabe, Mamoru.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 4 51-4, 04.2005.

Research output: Contribution to journalArticle

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, vol. 288, no. 4 51-4. https://doi.org/10.1152/ajpgi.00276.2004
Okada, Eriko ; Yamazaki, Motomi ; Tanabe, Masanobu ; Takeuchi, Tsutomu ; Nanno, Masanobu ; Oshima, Shigeru ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Nakamura, Tetsuya ; Kanai, Takanori ; Hibi, Toshifumi ; Watanabe, Mamoru. / IL-7 exacerbates chronic colitis with expansion of memory IL-7R high CD4+ mucosal T cells in mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 288, No. 4 51-4.
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AU - Okada, Eriko

AU - Yamazaki, Motomi

AU - Tanabe, Masanobu

AU - Takeuchi, Tsutomu

AU - Nanno, Masanobu

AU - Oshima, Shigeru

AU - Okamoto, Ryuichi

AU - Tsuchiya, Kiichiro

AU - Nakamura, Tetsuya

AU - Kanai, Takanori

AU - Hibi, Toshifumi

AU - Watanabe, Mamoru

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AB - 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.

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