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

作者：Geiger Theresa L; Abt Michael C; Gasteiger Georg; Firth Matthew A; O'Connor Margaret H; Geary Clair D; O'Sullivan Timothy E; van den Brink Marcel R; Pamer Eric G; Hanash Alan M; Sun Joseph C^*

来源：Journal of Experimental Medicine, 2014, 211(9): 1723-1731.

DOI：10.1084/jem.20140212

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.

• 出版日期2014-8-25