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Cell. 2016 May 19;165(5):1134-1146. doi: 10.1016/j.cell.2016.04.014. Epub 2016 May 5.

Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: mcolonna@pathology.wustl.edu.
3
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: eoltz@wustl.edu.

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.

PMID:
27156452
PMCID:
PMC4874868
DOI:
10.1016/j.cell.2016.04.014
[Indexed for MEDLINE]
Free PMC Article

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