IL-7 is essential for the development and the persistence of chronic colitis

Teruji Totsuka, Takanori Kanai, Yasuhiro Nemoto, Shin Makita, Ryuichi Okamoto, Kiichiro Tsuchiya, Mamoru Watanabe

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Although IL-7 has recently emerged as a key cytokine involved in controlling the homeostatic turnover and the survival of peripheral resting memory CD4+ T cells, its potential to be sustained pathogenic CD4+ T cells in chronic immune diseases, such as inflammatory bowel diseases, still remains unclear. In this study, we demonstrate that IL-7 is essential for the development and the persistence of chronic colitis induced by adoptive transfer of normal CD4+CD45RBhigh T cells or colitogeoic lamina propria (LP) CD4+ memory T cells into immunodeficient IL-7+/+ x RAG-1-/- and IL-7-/- x RAG-1-/- mice. Although EL-7+/+ x RAG-1-/- recipients transferred-with CD4+CD45RBhigh splenocytes developed massive inflammation of the large intestinal mucosa concurrent with massive expansion of Th1 cells, IL-7-/- x RAG-1-/- recipients did not. Furthermore, IL-7-/- x RAG-1-/-, but not IL-7+/+ x RAG-1-/-, mice transferred with LP CD4 +CD44highCD62L-IL-7Rαhigh effector-memory T cells (TEM) isolated from colitic CD4 +CD45RBhigh-transferred mice did not develop colitis. Although rapid proliferation of transferred colitogenic LP CD4+ TEM cells was observed in the in IL-7-/- x RAG-1 -/- mice to a similar extent of those in IL-7-/- x RAG-1-/- mice, Bcl-2 expression was significantly down-modulated in the transferred CD4+ T cells in IL-7-/- x RAG-1 -/- mice compared with those in IL-7+/+ x RAG-1 -/- mice. Taken together, IL-7 is essential for the development and the persistence of chronic colitis as a critical survival factor for colitogenic CD+ TEM cells, suggesting that therapeutic approaches targeting IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)4737-4748
Number of pages12
JournalJournal of Immunology
Volume178
Issue number8
DOIs
Publication statusPublished - 2007 Apr 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Totsuka, T., Kanai, T., Nemoto, Y., Makita, S., Okamoto, R., Tsuchiya, K., & Watanabe, M. (2007). IL-7 is essential for the development and the persistence of chronic colitis. Journal of Immunology, 178(8), 4737-4748. https://doi.org/10.4049/jimmunol.178.8.4737