國家衛生研究院 NHRI:Item 3990099045/14947
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    題名: Multidimensional analysis of lung lymph nodes in a mouse model of allergic lung inflammation following PM2.5 and indeno[1,2,3-cd]pyrene exposure
    作者: Liu, KY;Gao, Y;Xiao, W;Fu, J;Huang, S;Han, X;Hsu, SH;Xiao, X;Huang, SK;Zhou, Y
    貢獻者: National Institute of Environmental Health Sciences
    摘要: BACKGROUND: Ambient particulate matter with an aerodynamic diameter of  ≤ 2.5 μm (PM2.5) 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 PM2.5 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 PM2.5 and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. METHODS: PM2.5- 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 PM2.5 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 Il4 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 cells. DISCUSSION: These findings suggest that the PM2.5 (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 environment-disease causal relationship. https://doi.org/10.1289/EHP11580.
    日期: 2023-03
    關聯: Environmental Health Perspectives. 2023 Mar;131(3):Article number 37014.
    Link to: http://dx.doi.org/10.1289/ehp11580
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0091-6765&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000992724400018
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85151168304
    顯示於類別:[黃嘯谷] 期刊論文

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