Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens Academic Article uri icon


MeSH Major

  • Basic-Leucine Zipper Transcription Factors
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Lymphocyte Subsets


  • 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.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4144732

Digital Object Identifier (DOI)

  • 10.1084/jem.20140212

PubMed ID

  • 25113970

Additional Document Info

start page

  • 1723

end page

  • 31


  • 211


  • 9