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Aryl Hydrocarbon Receptor–Dependent Pathways in Immune Regulation
Author(s) -
Gargaro M.,
Pirro M.,
Romani R.,
Zelante T.,
Fallarino F.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13716
Subject(s) - aryl hydrocarbon receptor , immune system , cytotoxic t cell , transcription factor , immunology , mediator , microbiology and biotechnology , transplantation , cd8 , immune tolerance , t cell , acquired immune system , receptor , biology , medicine , in vitro , biochemistry , gene
The idea of possible involvement of the aryl hydrocarbon receptor (AhR) in transplant tolerance can be traced back >30 years, when very low doses of dioxin—the most potent AhR ligand—were found to markedly reduce the generation of cytotoxic T lymphocytes in response to alloantigen challenge in vivo . AhR is a ligand‐activated transcription factor that is activated by dioxins and other environmental pollutants. We now know that AhR can bind a broad variety of activating ligands that are disparate in nature, including endogenous molecules and those formed in the gut from food and bacterial products. Consequently, in addition to its classical role as a toxicological signal mediator, AhR is emerging as a transcription factor involved in the regulation of both innate and adaptive immune responses in various immune cell types, including lymphocytes and antigen‐presenting cells (APCs). Allograft rejection is mostly a T cell–mediated alloimmune response initiated by the recognition of alloantigens presented by donor and recipient APCs to recipient CD 4 + and CD 8 + T cells. Based on those findings, AhR may function as a critical sensor of outside and inside environments, leading to changes in the immune system that may have relevance in transplantation.