NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis.
Journal Article (Journal Article)
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.
- Kobayashi, T; Steinbach, EC; Russo, SM; Matsuoka, K; Nochi, T; Maharshak, N; Borst, LB; Hostager, B; Garcia-Martinez, JV; Rothman, PB; Kashiwada, M; Sheikh, SZ; Murray, PJ; Plevy, SE
- February 15, 2014
Volume / Issue
- 192 / 4
Start / End Page
- 1918 - 1927
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States