期刊
JOURNAL OF IMMUNOLOGY
卷 192, 期 4, 页码 1918-1927出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301819
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资金
- National Institutes of Health [R01 DK54452]
- National Gnotobiotic Rodent Resource Center [P40 RR018603]
- Center for Gastrointestinal Biology and Disease and Immunotechnologies, Gnotobiotic, and Histology Cores [P30 DK034987]
- Uehara Memorial Foundation
- American Gastroenterological Association's Research Scholars Award
- Crohn's and Colitis Foundation of America Research Fellowship Award
- Grants-in-Aid for Scientific Research [24590088, 25460960] Funding Source: KAKEN
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 Nfil(-/-) 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.
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