NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis

Taku Kobayashi, Erin C. Steinbach, Steven M. Russo, Katsuyoshi Matsuoka, Tomonori Nochi, Nitsan Maharshak, Luke B. Borst, Bruce Hostager, J. Victor Garcia-Martinez, Paul B. Rothman, Masaki Kashiwada, Shehzad Z. Sheikh, Peter J. Murray, Scott E. Plevy

研究成果: Article査読

29 被引用数 (Scopus)

抄録

NFIL3 is a transcription factor that regulates multiple immunologic functions. In myeloid cells, NFIL3 is IL-10 inducible and has a key role as a repressor of IL-12p40 transcription. NFIL3 is a susceptibility gene for the human inflammatory bowel diseases. In this article, we describe spontaneous colitis in Nfil3-/- mice. Mice lacking both Nfil3 and Il10 had severe early-onset colitis, suggesting that NFIL3 and IL-10 independently regulate mucosal homeostasis. Lymphocytes were necessary for colitis, because Nfil3/Rag1 double-knockout mice were protected from disease. However, Nfil3/Rag1 double-knockout mice adoptively transferred with wild-type CD4+ T cells developed severe colitis compared with Rag1-/- recipients, suggesting that colitis was linked to defects in innate immune cells. Colitis was abrogated in Nfil3/Il12b double-deficient mice, identifying Il12b dysregulation as a central pathogenic event. Finally, germ-free Nfil3 -/- mice do not develop colonic inflammation. Thus, NFIL3 is a microbiota-dependent, IL-10-independent regulator of mucosal homeostasis via IL-12p40.

本文言語English
ページ(範囲)1918-1927
ページ数10
ジャーナルJournal of Immunology
192
4
DOI
出版ステータスPublished - 2014 2 15
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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