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


ABSTRACT: 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 and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. We also uncover surprising features of STAT5 behavior, most notably the wholesale redistribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and genome-wide coordination with T-bet, another key TF in ILC biology. Collectively, our data position STAT5 as a central node in the TF network that instructs ILC development, homeostasis, and function and provide mechanistic insights on how it works at cellular and molecular levels.

SUBMITTER: Villarino AV 

PROVIDER: S-EPMC5626390 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Villarino Alejandro V AV   Sciumè Giuseppe G   Davis Fred P FP   Iwata Shigeru S   Zitti Beatrice B   Robinson Gertraud W GW   Hennighausen Lothar L   Kanno Yuka Y   O'Shea John J JJ  

The Journal of experimental medicine 20170915 10


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 and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the  ...[more]

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