NFIL3-Deficient Mice Develop Microbiota-Dependent, IL-12/23-Driven Spontaneous Colitis

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

来源：The Journal of Immunology, 2014, 192(4): 1918-1927.

DOI：10.4049/jimmunol.1301819

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.

• 出版日期2014-2-15