NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis.
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.
Duke Scholars
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- Tumor Necrosis Factor-alpha
- Th17 Cells
- Th1 Cells
- Microbiota
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Membrane Proteins
- Interleukin-23 Subunit p19
- Interleukin-12 Subunit p40
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Necrosis Factor-alpha
- Th17 Cells
- Th1 Cells
- Microbiota
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Membrane Proteins
- Interleukin-23 Subunit p19
- Interleukin-12 Subunit p40