LEADER 04416nam 2200445 450 001 9910136800803321 005 20230808192419.0 035 $a(CKB)3710000000631114 035 $a(oapen)https://directory.doabooks.org/handle/20.500.12854/43454 035 $a(EXLCZ)993710000000631114 100 $a20160411h20162016 fu 0 101 0 $aeng 135 $aurmn#---||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 04$aThe coevolution of IDO1 and AHR in the emergence of regulatory T cells in mammals$b[electronic resource] /$fedited by Ursula Grohmann and Paolo Puccetti 210 $cFrontiers Media SA$d2016 210 1$aLausanne, Switzerland :$cFrontiers Media SA,$d2016. 210 4$dİ2016 215 $a1 online resource (89 pages) $cillustrations, charts; digital, PDF file(s) 225 0 $aFrontiers research topics 300 $aPublished in Frontiers in Immunology. 311 $a2-88919-729-8 330 $aIndoleamine 2,3-dioxygenase (IDO1) is an ancestral enzyme that, initially confined to the regulation of tryptophan availability in local tissue microenvironments, is now considered to play a wider role that extends to homeostasis and plasticity of the immune system. Thus IDO biology has implications for many aspects of immunopathology, including viral infections, neoplasia, autoimmunity, and chronic inflammation. Its immunoregulatory effects are mainly mediated by dendritic cells (DCs) and involve not only tryptophan deprivation but also production of kynurenines that act on IDO? DCs, thus rendering an otherwise stimulatory DC capable of regulatory effects, as well as on T cells. The aryl hydrocarbon receptor (AhR) is a ligand-operated transcription factor originally recognized as the effector mediating the pathologic effects of dioxins and other pollutants. However, it is now well established that AhR activation by endogenous ligands can produce immunoregulatory effects. The IDO1 mechanism appears to have been selected through phylogenesis primarily to prevent overreacting responses to TLR-recognized pathogen-associated molecular patterns, and only later did it become involved in the response to T cell receptor-recognized antigens. As a result, in mammals, IDO1 has become pivotal in fetomaternal tolerance, at a time when regulatory T cells emerged to meet the same need, namely protecting the fetus. IDO1 and regulatory T (Treg) cells may have then coevolved to broaden their function well beyond their initial task of protecting the fetus, such that, in acquired immunity, IDO1 (with its dual enzymic and signaling function) has turned into an important component of the peripheral generation and effector function of regulatory T cells. AhR, in turn, which has a role in regulatory T-cell generation, is presumed to have evolved from invertebrates, where it served a ligand-independent role in normal development processes. Evolution of the receptor in vertebrates resulted in the ability to bind structurally different ligands, including xenobiotics and microbiota-derived catabolites. Considering the inability of invertebrate AhR homologs to bind dioxins, the adaptive role of the AhR to act as a regulator of xenobiotic-metabolizing enzymes may have been a vertebrate innovation, to later acquire an additional immune regulatory role by coevolutive pressure in mammals by IDO1 and regulatory T cells. Thus an entirely new paradigm in immunology, and more specifically in immune tolerance, is the coevolution of three systems, namely, the IDO1 mechanism, AhR-driven gene transcription, and T-cell regulatory activity, that originating from the initial need of protecting the fetus in mammals, have later turned into a pivotal mechanism of peripheral tolerance in autoimmunity, transplantation, and neoplasia. 606 $aImmunology 610 $aAryl hydrocarbon receptor (AhR) 610 $aindoleamine dioxygenase 1 and 2 (IDO1 and IDO2) 610 $atryptophan dioxygenase (TDO2) 610 $atryptophan metabolism 610 $aImmune Regulation 615 0$aImmunology. 700 $aUrsula Grohmann$4auth$01376090 702 $aGrohmann. Ursula 702 $aPuccetti$b Paolo 801 2$bUkMaJRU 906 $aBOOK 912 $a9910136800803321 996 $aThe coevolution of IDO1 and AHR in the emergence of regulatory T cells in mammals$93411381 997 $aUNINA