title: Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
abstract: Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been extensively studied in model organisms, little is known about these "first responders" in humans, especially their lineage and functional kinships to cytokine-secreting T helper (Th) cell counterparts. Here, we report gene regulatory circuitries for four human ILC-Th counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell-identity genes in each lineage, uncovering new modes of regulation for signature cytokines, new molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILC-Th subsets.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Koues
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Collins
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Robinette
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Porter
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Pyfrom
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Payton
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: mcolonna@pathology.wustl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: eoltz@wustl.edu.
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Oltz
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007694:Killer Cells, Natural; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D014066:Palatine Tonsil / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016207:Cytokines; D014157:Transcription Factors