Human Innate lymphoid cells

抄録

Innate lymphoid cells (ILCs) are a heterogeneous population of immune cells with two defining characteristics: 1) they have lymphoid origin, differentiating from the common lymphoid progenitor (CLP) and dependent on IL-2Rgc signaling. 2) They lack antigen-specific receptors and therefore do not require the RAG proteins for development. 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. We investigated gene regulatory circuitries for four human ILC-Th counterparts derived from mucosal environments. We found 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.