Cross-talk between Aryl Hydrocarbon Receptor and the Inflammatory Response

Aryl Hydrocarbon Receptor–Dependent Pathways in Immune Regulation

“…In another study, bone marrow-derived DCs stimulated with a synthetic AhR ligand, VAF347, were found to produce less IL-6, an effect that was suppressed in AhRdeficient DCs (20). These studies suggest that AhR in these cells may use a "noncanonical" (ARNT-independent) pathway instead of the canonical (ARNT-mediated) pathway, possibly through the recruitment of nuclear factor-jB family members (1). Understanding ligand-specific interaction with AhR in immune responses will be pivotal in explaining the subsequent AhR-dependent outcomes in immune responses.…”

“…Interestingly, activation of DCs with AhR ligands, such as TCDD or kynurenine, promotes the expression of the immunoregulatory indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 enzymes (1,10). Moreover, in response to lipopolisaccaride, AhR-deficient macrophages produced increased proinflammatory cytokines, and AhR-deficient DCs secreted less anti-inflammatory cytokine IL-10 (10).…”

“…The AhR-ARNT complex may then require additional coactivators, including members of other families of transcription factors, for its transcriptional activity (1). Widely expressed in a variety of animal species as well as in humans and initially credited with a specific function-hepatic clearance of xenobiotics, including dioxin-AhR has physiological functions that are only now beginning to be appreciated (2).…”

AhR: Far more than an environmental sensor

“…1,2 Signal molecules function as ligands for AhR, and activated AhR forms heterodimers at promoter recognition sequences of the target genes. The AhR/AhR nuclear translocator (ARNT) complex may then require coactivators (including members of other families of transcription factors) 3 in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase function. Within this scenario, 3 major factors appear to contribute to the outcome of gene transcriptional regulation by AhR, namely, nature of the ligand, local tissue microenvironment, and presence of coactivators in the cell.…”

Dysregulation of Notch and ERα signaling in AhR−/−male mice

“…AhR also plays important physiological functions such as in liver development, female reproduction, the immune system through regulating cell cycle, cell proliferation, cell apoptosis, cell differentiation, and inflammation (3)(4)(5). Studies have shown that AhR can interact with other signaling pathways including estrogen receptor, androgen receptor, and NF-κB signaling pathway (6)(7)(8)(9).…”