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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 2017-10, Vol.214 (10), p.2999-3014 |
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| cites | cdi_FETCH-LOGICAL-c478t-7166882f186dae85edcf3b1462c1f7f6012c16fc00eed2137a8636e7bfa5f7d3 |
| container_end_page | 3014 |
| container_issue | 10 |
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| container_title | The Journal of experimental medicine |
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| creator | Villarino, Alejandro V Sciumè, Giuseppe Davis, Fred P Iwata, Shigeru Zitti, Beatrice Robinson, Gertraud W Hennighausen, Lothar Kanno, Yuka O'Shea, John J |
| description | 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. |
| doi_str_mv | 10.1084/jem.20150907 |
| format | article |
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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.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20150907</identifier><identifier>PMID: 28916644</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Accumulation ; Animal tissues ; Animals ; Flow Cytometry ; Gene expression ; Gene Expression Profiling ; Genomes ; Homeostasis ; Homeostasis - physiology ; Immunity, Cellular - physiology ; Immunity, Innate - physiology ; Interfaces ; Interleukin 15 ; Killer Cells, Natural - metabolism ; Killer Cells, Natural - physiology ; Lymphocytes - physiology ; Lymphoid cells ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Natural killer cells ; Signaling ; Stat5 protein ; STAT5 Transcription Factor - genetics ; STAT5 Transcription Factor - physiology ; Transcription factors</subject><ispartof>The Journal of experimental medicine, 2017-10, Vol.214 (10), p.2999-3014</ispartof><rights>This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.</rights><rights>Copyright Rockefeller University Press Oct 2, 2017</rights><rights>This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-7166882f186dae85edcf3b1462c1f7f6012c16fc00eed2137a8636e7bfa5f7d3</citedby><cites>FETCH-LOGICAL-c478t-7166882f186dae85edcf3b1462c1f7f6012c16fc00eed2137a8636e7bfa5f7d3</cites><orcidid>0000-0001-8319-9841 ; 0000-0002-6456-9752 ; 0000-0001-8068-2176 ; 0000-0003-0131-512X ; 0000-0003-4610-7535</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626390/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626390/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28916644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Villarino, Alejandro V</creatorcontrib><creatorcontrib>Sciumè, Giuseppe</creatorcontrib><creatorcontrib>Davis, Fred P</creatorcontrib><creatorcontrib>Iwata, Shigeru</creatorcontrib><creatorcontrib>Zitti, Beatrice</creatorcontrib><creatorcontrib>Robinson, Gertraud W</creatorcontrib><creatorcontrib>Hennighausen, Lothar</creatorcontrib><creatorcontrib>Kanno, Yuka</creatorcontrib><creatorcontrib>O'Shea, John J</creatorcontrib><title>Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>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. 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Villarino and G. Sciumè contributed equally to this paper.</notes><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.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>28916644</pmid><doi>10.1084/jem.20150907</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8319-9841</orcidid><orcidid>https://orcid.org/0000-0002-6456-9752</orcidid><orcidid>https://orcid.org/0000-0001-8068-2176</orcidid><orcidid>https://orcid.org/0000-0003-0131-512X</orcidid><orcidid>https://orcid.org/0000-0003-4610-7535</orcidid><oa>free_for_read</oa></addata></record> |
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| source | PubMed Central |
| subjects | Accumulation Animal tissues Animals Flow Cytometry Gene expression Gene Expression Profiling Genomes Homeostasis Homeostasis - physiology Immunity, Cellular - physiology Immunity, Innate - physiology Interfaces Interleukin 15 Killer Cells, Natural - metabolism Killer Cells, Natural - physiology Lymphocytes - physiology Lymphoid cells Mice Mice, Inbred C57BL Mice, Knockout Natural killer cells Signaling Stat5 protein STAT5 Transcription Factor - genetics STAT5 Transcription Factor - physiology Transcription factors |
| title | Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells |
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