NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1918-1927
Number of pages10
JournalJournal of Immunology
Volume192
Issue number4
DOIs
Publication statusPublished - 2014 Feb 15

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Interleukin-23
Microbiota
Colitis
Interleukin-12
Interleukin-10
Interleukin-12 Subunit p40
Knockout Mice
Homeostasis
Myeloid Cells
Inflammatory Bowel Diseases
Transcription Factors
Lymphocytes
Inflammation
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Kobayashi, T., Steinbach, E. C., Russo, S. M., Matsuoka, K., Nochi, T., Maharshak, N., ... Plevy, S. E. (2014). NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis. Journal of Immunology, 192(4), 1918-1927. https://doi.org/10.4049/jimmunol.1301819

NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis. / 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.

In: Journal of Immunology, Vol. 192, No. 4, 15.02.2014, p. 1918-1927.

Research output: Contribution to journalArticle

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 2014, 'NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis', Journal of Immunology, vol. 192, no. 4, pp. 1918-1927. https://doi.org/10.4049/jimmunol.1301819
Kobayashi T, Steinbach EC, Russo SM, Matsuoka K, Nochi T, Maharshak N et al. NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis. Journal of Immunology. 2014 Feb 15;192(4):1918-1927. https://doi.org/10.4049/jimmunol.1301819
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. / NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis. In: Journal of Immunology. 2014 ; Vol. 192, No. 4. pp. 1918-1927.
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