Aryl hydrocarbon receptor in mesenchymal stromal cells: new frontiers in AhR biology

FEBS J. 2021 Jul;288(13):3962-3972. doi: 10.1111/febs.15599. Epub 2020 Nov 1.

Abstract

Mesenchymal stromal cells (MSCs) are nonhematopoietic cells that have been clinically explored as investigational cellular therapeutics for tissue injury regeneration and immune-mediated diseases. Their pharmaceutical properties arise from activation of endogenous receptors and transcription factors leading to a paracrine effect which mirror the biology of progenitors from which they arise. The aryl hydrocarbon receptor (AhR) is a transcription factor that has been extensively studied as an environmental sensor for xenobiotics, but recent findings suggest it can modulate immunological functions. Both genetic and pharmacological investigations revealed that MSCs express AhR and that it plays roles in inflammation, immunomodulation, and mesodermal plasticity of endogenous MSCs. Further, AhR has been shown to interact with key signaling cascades associated with these conditions. Therefore, AhR has potential to be an attractive target in both endogenous and culture-adapted MSCs for novel therapeutics to treat inflammation and other age-related disorders.

Keywords: aryl hydrocarbon receptor; cell therapy; mesenchymal stromal cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Biphenyl Compounds / metabolism
  • Humans
  • Ligands
  • Mesenchymal Stem Cells / metabolism*
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Shock, Septic / genetics
  • Shock, Septic / metabolism
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Biphenyl Compounds
  • Ligands
  • Polycyclic Aromatic Hydrocarbons
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • diphenyl