ROR is required for expansion and memory maintenance of ILC1s via a lymph node-liver axis

Type 1 innate lymphoid cells (ILC1s) possess adaptive immune features, which confer antigen -specific memory responses against haptens and viruses. However, the transcriptional regulation of memory ILC1 responses is currently not known. We show that retinoic acid receptor -related orphan receptor alpha (RORa) has high expression in memory ILC1s in murine contact hypersensitivity (CHS) models. RORa deficiency diminishes ILC1-mediated CHS responses significantly but has no effect on memory T cell -mediated CHS responses. During sensitization, RORa promotes sensitized-ILC1 expansion by suppressing expression of cell -cycle repressors in draining lymph nodes. RORa programs gene -expression patterns related to cell survival and is required for the long-term maintenance of memory ILC1s in the liver. Our findings reveal RORa to be a key transcriptional factor for sensitized-ILC1 expansion and long-term maintenance of memory ILC1s.