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

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Geiger, TL; Abt, MC; Gasteiger, G; Firth, MA; O'Connor, MH; Geary, CD; O'Sullivan, TE; van den Brink, MR; Pamer, EG; Hanash, AM; ...Date
2014-08-25Source Title
Journal of Experimental MedicinePublisher
Rockefeller University PressUniversity of Melbourne Author/s
Firth, MatthewAffiliation
Medical Biology (W.E.H.I.)Metadata
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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. (2014). Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens.. J Exp Med, 211 (9), pp.1723-1731. https://doi.org/10.1084/jem.20140212.Access Status
Open AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144732Abstract
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.
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