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

Cell Rep. 2024 Feb 27;43(2):113786. doi: 10.1016/j.celrep.2024.113786. Epub 2024 Feb 15.

Abstract

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 (RORα) has high expression in memory ILC1s in murine contact hypersensitivity (CHS) models. RORα deficiency diminishes ILC1-mediated CHS responses significantly but has no effect on memory T cell-mediated CHS responses. During sensitization, RORα promotes sensitized-ILC1 expansion by suppressing expression of cell-cycle repressors in draining lymph nodes. RORα 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 RORα to be a key transcriptional factor for sensitized-ILC1 expansion and long-term maintenance of memory ILC1s.

Keywords: CP: Immunology; RORα; immunological memory; transcriptional regulation; type 1 innate lymphoid cells.

MeSH terms

  • Animals
  • Cell Survival
  • Immunity, Innate*
  • Liver
  • Lymph Nodes
  • Lymphocytes*
  • Mice
  • Transcription Factors

Substances

  • Transcription Factors
  • Rora protein, mouse