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Background: Environmental exposure to peanut through non‐oral routes is a risk factor for peanut allergy. Early‐life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model. Methods: C57BL/6J mice were co‐exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut‐specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM‐induced peanut allergy. Results: Airway co‐exposure to peanut and either UPM‐ or DEP‐induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut‐specific CD4+ Th cells. UPM‐ and DEP‐induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM‐ and DEP‐induced peanut allergy, whereas TLR4 signaling was dispensable. DEP‐induced peanut allergy and Tfh‐cell differentiation depended on IL‐1 but not IL‐33 signaling, whereas neither cytokine alone was necessary for UPM‐mediated sensitization. Conclusion: Environmental co‐exposure to peanut and PM induces peanut‐specific Tfh cells and peanut allergy in mice. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as ABO and TNFRSF14 , and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD., Competing Interests: Competing interests The authors declare no competing interests.