Aryl hydrocarbon receptor-Interleukin-22 axis in Group 3 innate lymphoid cells (AhR/IL-22/ILC3 axis)

The Aryl hydrocarbon receptor (AhR)-Interleukin-22 (IL-22) axis in Group 3 innate lymphoid cells (ILC3s) is a critical signaling pathway for maintaining mucosal homeostasis and barrier integrity, particularly in the gastrointestinal tract and skin (Lee et al., 2012, Nature Immunology; Kiss et al., 2011, Science). AhR is a ligand-activated transcription factor that senses environmental, dietary, and microbial signals, such as indole derivatives, to regulate the development and effector functions of ILC3s (Zelante et al., 2013, Immunity). Upon activation, AhR promotes the robust production of IL-22 by ILC3s, which subsequently acts on epithelial cells to induce the expression of antimicrobial peptides and promote tissue repair (Sonnenberg et al., 2011, Immunity). Dysregulation of this pathway is strongly linked to the pathogenesis of inflammatory bowel disease (IBD), where a deficiency in IL-22-producing ILC3s can lead to impaired barrier function and chronic inflammation (Geremia et al., 2011, JEM). Therapeutic strategies targeting this axis include AhR agonists like tapinarof and IL-22-Fc fusion proteins, which aim to restore epithelial health and suppress inflammatory responses in conditions like psoriasis and IBD (Sabat et al., 2014, Nature Reviews Drug Discovery).

Other names

AhR-IL-22 pathwayAryl hydrocarbon receptor-Interleukin-22 signaling axisILC3-derived IL-22 pathwayAhR-ILC3-IL-22 axis

The pathway is activated when exogenous or endogenous ligands bind to the Aryl hydrocarbon receptor (AhR) within Group 3 innate lymphoid cells (ILC3s), triggering the transcription and secretion of Interleukin-22 (IL-22). IL-22 then binds to the IL-22 receptor complex (comprising IL-22R1 and IL-10R2) on non-hematopoietic epithelial cells, activating the STAT3 signaling pathway to promote cell proliferation, survival, and the production of antimicrobial peptides such as Reg3 gamma.