Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation.

ABSTRACT: Innate lymphoid cells (ILCs) include cytotoxic natural killer cells and distinct groups of cytokine-producing innate helper cells which participate in immune defense and promote tissue homeostasis. Circulating human ILC precursors (ILCP) able to generate all canonical ILC subsets via multi-potent or uni-potent intermediates according to our previous work. Here we show potential cooperative roles for the Notch and IL-23 signaling pathways for human ILC differentiation from blood ILCP using single cell cloning analyses and validate these findings in patient samples with rare genetic deficiencies in IL12RB1 and RORC. Mechanistically, Notch signaling promotes upregulation of the transcription factor RORC, enabling acquisition of Group 1 (IFN-γ) and Group 3 (IL-17A, IL-22) effector functions in

SUBMITTER: Croft CA 

PROVIDER: S-EPMC9329340 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature