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

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.