Fiche publication
Date publication
juillet 2016
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan
,
Dr KASTNER Philippe
Tous les auteurs :
Li S, Heller JJ, Bostick JW, Lee A, Schjerven H, Kastner P, Chan S, Chen ZE, Zhou L
Lien Pubmed
Résumé
Group 3 innate lymphoid cells (ILC3s) expressing the transcription factor (TF) RORγt are important for the defense and homeostasis of host intestinal tissues. The zinc finger TF Ikaros, encoded by Ikzf1, is essential for the development of RORγt(+) fetal lymphoid tissue inducer (LTi) cells and lymphoid organogenesis, but its role in postnatal ILC3s is unknown. Here, we show that small-intestinal ILC3s had lower Ikaros expression than ILC precursors and other ILC subsets. Ikaros inhibited ILC3s in a cell-intrinsic manner through zinc-finger-dependent inhibition of transcriptional activity of the aryl hydrocarbon receptor, a key regulator of ILC3 maintenance and function. Ablation of Ikzf1 in RORγt(+) ILC3s resulted in increased expansion and cytokine production of intestinal ILC3s and protection against infection and colitis. Therefore, in contrast to being required for LTi development, Ikaros inhibits postnatal ILC3 development and function to regulate gut immune responses at steady state and in disease.
Référence
Immunity. 2016 Jul;45(1):185-97
