Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens Journal Article
| Authors: | Geiger, T. L.; Abt, M. C.; Gasteiger, G.; Firth, M. A.; O'Connor, M. H.; Geary, C. D.; O'sullivan, T. E.; Van Den Brink, M. R.; Pamer, E. G.; Hanash, A. M.; Sun, J. C. |
| Article Title: | Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens |
| 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. © 2014 Geiger et al. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; protein function; animal cell; mouse; bone marrow; cell maturation; animal experiment; animal model; inflammation; cell lineage; lung; innate immunity; intestine flora; basic leucine zipper transcription factor; bacterial infection; clostridium difficile; infection sensitivity; host; lymphoid cell; citrobacter rodentium; intraabdominal fat; microbial community; priority journal; article; natural cytotoxicity triggering receptor 1; transcription factor nfil3; lymphoid tissue inducer like cell; type 1 innate lymphoid cell; type 2 innate lymphoid cell; type 3 innate lymphoid cell |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 211 |
| Issue: | 9 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2014-08-25 |
| Start Page: | 1723 |
| End Page: | 1731 |
| Language: | English |
| DOI: | 10.1084/jem.20140212 |
| PROVIDER: | scopus |
| PMCID: | PMC4144732 |
| PUBMED: | 25113970 |
| DOI/URL: | |
| Notes: | Export Date: 1 October 2014 -- Source: Scopus |
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