Ahr activation of MSC either by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or cockroach allergen upregulates the expression of inducible nitric oxide synthase (iNOS) and secretion of nitric oxide (NO) and Tgf- leading to the inhibition of the T cell response. activation by particle-associated polycyclic aromatic hydrocarbons from the environment is pro-inflammatory, inducing mucus hypersecretion, airway remodelling, dysregulation of antigen presenting cells and exacerbates asthma features. Data concerning the role of AhR in cells from asthmatic patients are also reviewed, since AhR could represent a potential target for therapeutic immunomodulation. (Cytochrome P450, family 1, subfamily A, polypeptide 1) is a hallmark of AhR signalling. CYP1A1 protein is a member of Stachyose tetrahydrate the cytochrome P450 superfamily of enzymes which one of their Stachyose tetrahydrate roles is to degrade the AhR natural ligands. Numerous genes coding for pro-inflammatory and anti-inflammatory products are induced by this mechanism, which is referred to as the AhR genomic pathway. Non-genomic pathways are also described such as interactions of AhR with other transcription factors or modulation of calcium transport. Altogether these AhR pathways are able to control positively or negatively the immune response. 1.2. AhR Ligands Different exogenous AhR ligands have been identified including not only classic xenobiotic AhR agonists Stachyose tetrahydrate (such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs)) , but also bacterial pigments from Pseudomonas aeruginosa and Mycobacterium tuberculosis , and even allergens ( and unpublished data). Endogenous ligands include tryptophan metabolites like the 6-formylindolo[3,2-b]carbazole (FICZ), the kynurenines, ligands provided by commensal microbiota , dietary components derived from vegetables  and other metabolites such as bilirubin and arachidonic acid derivatives [12,13]. The AhR ligands discussed in this review are listed in Table 1. Recent data have shown that AhR is critical for a wide range of immune functions including the Rabbit Polyclonal to EIF3J maintenance of innate and adaptive cell populations at mucosal barrier sites, and the control of inflammation at steady-state or during ongoing inflammatory responses, such as asthma. Table 1 List of discussed AhR ligands. results in ILC2 suppression but promotes ILC3 function [58,59,60,61], suggesting that Ahr favours Th17-type cytokine production by subtle counter regulation in ILC subsets at least at the gut level. Although several studies have shown that AhR ligands containing pollutants induce Th17-type responses, no study has yet explored their effects on lung ILC3. Some forms of asthma exhibit a Th17 high profile that may contribute to their severity, whereas the induction of Treg is considered as beneficial. AhR manifestation varies in different T cell subsets, with levels becoming the highest in Th17 and Treg cells, Stachyose tetrahydrate and the lowest in Th1 and Th2 cells . It was only in the 2000 s that AhR required a central place in the rules of T cell biology. It was demonstrated that AhR is definitely upregulated in developing Th17 cells, and boosts the production of Il-17 and Il-22 [63,64,65] in mice and of IL-22 in humans [66,67]. Accordingly, deficient mice show decreased Il-22 production by Th17 cells . However, Ahr ligands may differentially effect Th17-mediated disease results with FICZ favouring and TCDD inhibiting this profile [64,65]. Ahr manifestation is definitely induced by transmission transducer and activation of transcription 3 during Th17 differentiation , and it suppresses Stat5 and Stat1 signalling that interferes with Th17 generation permitting a positive opinions loop . Collectively, Ahr appears to play a role in the early phases of Th17 differentiation, whereas the development of fully pathogenic effector Th17 cells requires additional factors . However, Forkhead package P3 (FOXP3)+ T regulatory cells (Treg) and IL-10 Stachyose tetrahydrate generating type 1 T regulatory cells (Tr1) cells have also been linked to AhR activation [70,71]. In contrast to FICZ that promotes Th17 differentiation, AhR ligands such as TCDD or kynurenine increase manifestation through different mechanisms including epigenetic modifications of T cells and modulation of DC [15,72]. These epigenetic modifications of T cells, in particular DNA methylation, allows differentiation of different sub-populations and contributes to flexibility and plasticity among CD4+ T cell subsets . In asthma individuals, improved methylation of in peripheral blood Treg cells has been associated with their practical impairment in an environment of high ambient air pollution levels compared to asthmatic individuals with low air pollution levels . For Tr1 cells, it has been shown that their Ahr manifestation is definitely boosted by Il-27, a pleiotropic cytokine with diverse immune regulatory activities, through a mechanism driven by Stat3 . This activation influences the transcriptional system of Tr1 cells leading to the production of the immunosuppressive cytokine Il-10. It is noteworthy.