A -element at the locus regulates the development of type 3 innate lymphoid cells.

BACKGROUND

As an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether -acting elements regulate RORγt expression in ILC3s is unknown.

RESULTS

Here we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4NKp46 ILC3 population, though the overall numbers and frequencies of RORγt ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4NKp46 ILC3 subset.

CONCLUSION

Our study thus identifies CNS9 as an essential -regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.