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J Exp Med. 2014 Aug 25;211(9):1723-31. doi: 10.1084/jem.20140212. Epub 2014 Aug 11.

Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens.

Author information

1
Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
2
Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065.
3
Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065.
4
Immunology Program; Adult Bone Marrow Transplant Service and Infectious Diseases Service, Department of Medicine; and Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065 sunj@mskcc.org.

Abstract

The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the development of natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). We find that Nfil3 plays a critical role in the development of other mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including lymphoid tissue inducer (LTi)-like cells, are severely diminished in both numbers and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises intestinal innate immune defense against acute bacterial infection with Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a loss of the recently identified ILC precursor, yet conditional ablation of Nfil3 in the NKp46(+) ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3 is required early during ILC3 development but not for lineage maintenance. Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement for Nfil3 in the development of all ILC lineages.

PMID:
25113970
PMCID:
PMC4144732
DOI:
10.1084/jem.20140212
[Indexed for MEDLINE]
Free PMC Article

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