The transcription factor RORα is required for the development of type 1 innate lymphoid cells in adult bone marrow.

Abstract

Type 1 innate lymphoid cells (ILC1s) respond to infections and tumors by producing IFN-γ. Although RAR-related orphan receptor α (RORα) is required for ILC2s and some ILC3s, its role in ILC1 development remains controversial. To investigate the role of RORα in ILC1s, we analyzed bone marrow (BM) chimeras of RORα-deficient mice. ILC1s derived from RORα-deficient BM cells were significantly reduced in various tissues, including the intestine, indicating a hematopoietic cell-intrinsic need for RORα in ILC1 development. Developmental stage-specific RORα-deficient mice showed a decrease in adult liver and BM IL-7R+ ILC1s and an increase in BM NK cells, whereas fetal liver ILC1s and adult liver IL-7R- ILC1s remained unchanged. Furthermore, RORα is primarily required for IL-7R+ precursor stages and partially affects small intestine ILC1 after differentiation. This study suggests that RORα promotes ILC1 differentiation while suppressing NK cell differentiation at the ILC precursor stage in the adult BM.