Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells
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 hi...
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Published in | The Journal of experimental medicine Vol. 214; no. 10; pp. 2999 - 3014 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
02.10.2017
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 A.V. Villarino and G. Sciumè contributed equally to this paper. |
ISSN: | 0022-1007 1540-9538 |
DOI: | 10.1084/jem.20150907 |