Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells

• DOI: 10.1084/jem.20150907
• Publication Date: 2017-09-15T14:10:12Z
• Authors: Alejandro V. Vill...; Giuseppe Sciumè; Fred P. Davis; Shigeru Iwata; Beatrice Zitti; Gertraud W. Robinson; Lothar Hennighausen; Yuka Kanno; John J. O’Shea
• Keywords: STAT5; Innate lymphoid cell

Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice reveal hierarchy dependency populating nonlymphoid tissues. We apply transcriptome genomic distribution analyses define gene signature natural killer (NK) cells, prototypical subset, provide systems-based molecular rationale its key functions downstream IL-15. also uncover surprising features behavior, most notably wholesale redistribution occurs when NK shift from tonic signaling acute cytokine-driven signaling, genome-wide coordination with T-bet, another TF biology. Collectively, our data position as central node network instructs development, homeostasis, function mechanistic insights on how it works at cellular levels.