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Smoking has caused great public health burdens in the global. Although socioeconomic factors have been confirmed to substantially influence smoking behaviors, the impact of comprehensive social deprivations on smoking behavior and related biological mechanisms are still unclear. Supported by UK Biobank cohort, we randomly divided 369,915 participants into discovery cohort (60%) and replication cohort (40%). We first tested the associations for index of multiple deprivation (IMD) and 7 IMD subdomains with ever-smoking and daily smoking frequency using regression models in both cohorts. Genome-wide by environment interaction study (GWEIS) was further conducted by using PLINK2.0 to detect the effects of the interactions between SNPs and IMD subdomains on two smoking behaviors. In discovery and replication cohorts, we observed the more deprivation status the individuals were in, the higher daily smoking frequency or risk to be ever smokers. And among the subdomains of IMD, income, education, health, living environment, and crime deprivation were positively associated with the risk of smoking behaviors, while employment deprivation was negatively correlated with smoking behaviors (all P < 0.0125). Totally, GWEIS analysis detected 23 shared significant socioeconomic-deprivation interacted loci for daily smoking frequency in two cohorts, such as rs116680599 at 2p16.3 (NRXN1, Pdiscovery = 7.68 × 10−14, Preplication = 1.96 × 10−2) and rs150451424 at 16p13.3 (RBFOX1, Pdiscovery = 1.89 × 10−10, Preplication = 1.96 × 10−2) interacting with employment deprivation. We illustrated the diverse effects of IMD on smoking behaviors and provided insights for the biological mechanisms of the interaction effects between socioeconomic deprivation with genetic factors on smoking behaviors. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4+ T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4+Foxp+ Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation. [ABSTRACT FROM AUTHOR]