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The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10–2.31 and AOR=1.60, 95%CI=1.06–2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not. [ABSTRACT FROM AUTHOR]

Background: Exposure to environmental pollutants, including benzo[a]pyrene (BaP), has been implicated in allergic diseases and intestinal microbiota homeostasis, but the environment-microbiota-immunity triangular relationship and to what extent BaP-induced remodeling of the gut microbiota contributes to intestinal allergic inflammation remain to be established. Objectives: We investigated the impact of BaP on intestinal allergic inflammation and examined the relationship between this effect and gut microbiota dysbiosis. We explored the potential ability of intestinal bacteria to degrade BaP and alleviate cytotoxicity as a detoxification strategy to counteract the effects of BaP exposure. Methods: We combined microbiome shotgun metagenomics with animal histological and intestinal allergic inflammatory responses to assess the effects of BaP (50 [micro]g/mouse per day) in a 23-d toxicity test in antigen-induced allergic female mice. In addition, genome annotation, quantitative analysis of BaP, and in vitro cytotoxicity-tests using CaCo-2 cells were conducted to infer the role of intestinal bacteria in BaP detoxification. Results: BaP exposure impacted the taxonomic composition and the functional potential of the gut microbiota and aggravated antigen-induced intestinal allergic inflammatory responses. The level of inflammatory cytokines correlated with the abundance of specific bacterial taxa, including Lachnospiraceae bacterium 28-4 and Alistipes inops. We identified 614 bacteria harboring genes implicated in the degradation of BaP, and 4 of these bacterial strains were shown to significantly reduce the cytotoxicity of BaP to CaCo-2 cells in vitro. Discussion: Using allergic female mice as a model, we investigated the relationship between BaP, microbiota, and host immune reactions, highlighting the role of gut bacteria in BaP-aggravated allergic reactions. Our findings offer novel insight toward establishing the causal relationship between BaP exposure and the occurrence of allergic disorders. Identifying gut bacteria that degrade BaP may provide new strategies for ameliorating BaP cytotoxicity. https://doi.org/10.1289/EHP11874, Introduction Polycyclic aromatic hydrocarbons (PAHs) are a large group of chemicals with two or more fused aromatic rings. (1,2) Benzo[a]pyrene (BaP), a model compound for PAHs, causes great environmental problems [...]

BACKGROUND: Ambient particulate matter with an aerodynamic diameter of [less than or equal to]2.5 [micro]m (P[M.sub.2.5]) is suggested to act as an adjuvant for allergen-mediated sensitization and recent evidence suggests the importance of T follicular helper (Tfh) cells in allergic diseases. However, the impact of P[M.sub.2.5] exposure and its absorbed polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains unknown. OBJECTIVES: We aimed to explore the impact of environmental P[M.sub.2.5] and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. METHODS: P[M.sub.2.5]- or IP-mediated remodeling of cellular composition in lung lymph nodes (LNs) was determined by mass cytometry in a house dust mite (HDM)-induced mouse allergic lung inflammation model. The differentiation and function of Tfh cells in vitro were analyzed by flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, immunoprecipitation, and western blot analyses. RESULTS: Mice exposed to P[M.sub.2.5] during the HDM sensitization period demonstrated immune cell population shifts in lung LNs as compared with those sensitized with HDM alone, with a greater number of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) response and pulmonary inflammation. Similarly enhanced phenotypes were also found in mice exposed to IP and sensitized with HDM. Further, IP administration was found to induce interleukin-21 (Il21) and 114 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient [CD4.sup.+] T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the 1121 and Il4 promoters in differentiated Tfh2 cells. DISCUSSION: These findings suggest that the P[M.sub.2.5] (IP)-AhR-c-Maf axis in Tfh2 cells was important in allergen sensitization and lung inflammation, thus adding a new dimension in the understanding of Tfh2 cell differentiation and function and providing a basis for establishing the environmentdisease causal relationship. https://doi.org/10.1289/EHP11580, Introduction T helper 2 (Th2) cells have long been considered to mainly regulate the pathogenic manifestations of allergic asthma, such as immunoglobulin E (IgE)-mediated sensitization, airway hyperresponsiveness, and eosinophil infiltration. [...]