Epigenomic regulation of macrophage polarization: Where do the nuclear receptors belong?

Immunol Rev. 2023 Aug;317(1):152-165. doi: 10.1111/imr.13209. Epub 2023 Apr 19.

Abstract

Our laboratory has a long-standing research interest in understanding how lipid-activated transcription factors, nuclear hormone receptors, contribute to dendritic cell and macrophage gene expression regulation, subtype specification, and responses to a changing extra and intracellular milieu. This journey in the last more than two decades took us from identifying target genes for various RXR heterodimers to systematically mapping nuclear receptor-mediated pathways in dendritic cells to identifying hierarchies of transcription factors in alternative polarization in macrophages to broaden the role of nuclear receptors beyond strictly ligand-regulated gene expression. We detail here the milestones of the road traveled and draw conclusions regarding the unexpectedly broad role of nuclear hormone receptors as epigenomic components of dendritic cell and macrophage gene regulation as we are getting ready for the next challenges.

Keywords: EGR2; IL-4; PPARγ; STAT6; epigenome; macrophage; nuclear receptors; polarization; transcriptional regulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Epigenomics*
  • Gene Expression Regulation
  • Humans
  • Macrophages / metabolism
  • Receptors, Cytoplasmic and Nuclear* / genetics
  • Receptors, Cytoplasmic and Nuclear* / metabolism
  • Transcription Factors

Substances

  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors