The impact of monthly air pollution exposure and its interaction with individual factors: Insight from a large cohort study of comprehensive hospitalizations in Guangzhou area

BackgroundAlthough the association between short-term air pollution exposure and certain hospitalizations has been well documented, evidence on the effect of longer-term (e. g., monthly) air pollution on a comprehensive set of outcomes is still limited.MethodA total of 68,416 people in South China were enrolled and followed up during 2019–2020. Monthly air pollution level was estimated using a validated ordinary Kriging method and assigned to individuals. Time-dependent Cox models were developed to estimate the relationship between monthly PM10 and O3 exposures and the all-cause and cause-specific hospitalizations after adjusting for confounders. The interaction between air pollution and individual factors was also investigated.ResultsOverall, each 10 μg/m3 increase in PM10 concentration was associated with a 3.1% (95%CI: 1.3%−4.9%) increment in the risk of all-cause hospitalization. The estimate was even greater following O3 exposure (6.8%, 5.5%−8.2%). Furthermore, each 10 μg/m3 increase in PM10 was associated with a 2.3%-9.1% elevation in all the cause-specific hospitalizations except for those related to respiratory and digestive diseases. The same increment in O3 was relevant to a 4.7%−22.8% elevation in the risk except for respiratory diseases. Additionally, the older individuals tended to be more vulnerable to PM10 exposure (Pinteraction: 0.002), while the alcohol abused and those with an abnormal BMI were more vulnerable to the impact of O3 (Pinteraction: 0.052 and 0.011). However, the heavy smokers were less vulnerable to O3 exposure (Pinteraction: 0.032).ConclusionWe provide comprehensive evidence on the hospitalization hazard of monthly PM10 and O3 exposure and their interaction with individual factors

IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation

Acute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model. In contrast, IL-17C overexpression ameliorated aGVHD. IL-17C deficiency increased intestinal epithelial permeability and elevated inflammatory cytokine production, leading to an enhanced aGVHD progression. Tregs was reduced in recipients of IL-17C−/− graft, whilst restored after IL-17C overexpression. Decreased Treg differentiation was abrogated after neutralizing IFN-γ, but not IL-6. Moreover, depletion of Tregs diminished the protective effect of IL-17C. Of note, patients with low IL-17C expression displayed higher aGVHD incidence together with poor overall survival, thereby IL-17C could be an independent risk factor for aGVHD development. Our results are the first demonstrating the protective role of IL-17C in aGVHD by promoting intestinal barrier functions and Treg differentiation in a MHC fully mismatched murine aGVHD model. IL-17C may serve as a novel biomarker and potential therapeutic target for aGVHD