Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells
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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 STAT5 is critical for accumulation of all known ILC subsets in mice, and reveal a hierarchy of STAT5 dependency for populating lymphoid and non-lymphoid tissues. We also apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in NK cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. Additionally, we uncover surprising features of STAT5 behavior, most notably, the wholesale re-distribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and its genome-wide coordination with T-bet, another key transcription factor in ILC biology. Collectively, our data position STAT5 as a central node in the transcription factor network that instructs ILC development, homeostasis and function, and provide mechanistic insights on how it works at cellular and molecular levels.
ORGANISM(S): Mus musculus
PROVIDER: GSE100674 | GEO | 2017/09/13
SECONDARY ACCESSION(S): PRJNA392693
REPOSITORIES: GEO
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