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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 15, 2014

Published In

Volume / Issue

  • 192 / 4

Start / End Page

  • 1918 - 1927

PubMed ID

  • 24442434

Pubmed Central ID

  • PMC3948213

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1301819


  • eng

Conference Location

  • United States