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PM2.5, a major environmental pollutant, and high relative humidity frequently coexist in urban and industrialized regions, particularly when ventilation is poor. However, the combined effects of PM2.5 and humidity remain unclear. This study used a murine asthma model, exposing male Balb\/c mice sensitized with ovalbumin (OVA) to PM2.5 (75 \u03bcg\/m3 and 35 \u03bcg\/m3), based on China\u2019s Ambient Air Quality Standards (GB3095-2012), and\/or varying relative humidity levels in a controlled chamber. Allergic asthma severity was evaluated through histopathological changes, pulmonary function, Th1\/Th2 balance, mucus hypersecretion, and inflammatory factor levels, alongside the activation of TRPV4 and MAPK signaling pathways (ERK, p38MAPK, and JNK). The results showed that high humidity (90%) or PM2.5 exposure alone had minimal impact, but combined exposure to 75 \u03bcg\/m3 PM2.5 and 90% humidity markedly aggravated airway hyperresponsiveness, inflammation, and mucus hypersecretion. These changes coincided with enhanced TRPV4 activation and MAPK signaling, particularly p38MAPK and JNK, while ERK1\/2 remained unaffected. A lower PM2.5 concentration (35 \u03bcg\/m3) combined with 90% humidity had a weaker impact. Blocking TRPV4 with HC-067047 effectively mitigated asthma exacerbation caused by combined exposure. These findings demonstrate that co-exposure to PM2.5 and high humidity dose-dependently exacerbates allergic asthma, an effect likely mediated by TRPV4-MAPK pathway activation. Targeting TRPV4 may offer a potential therapeutic strategy to mitigate asthma exacerbation in environments with high humidity and PM2.5.<\/jats:p>","DOI":"10.3390\/toxics14030219","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:15:29Z","timestamp":1772550929000},"page":"219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Synergistic Effects of Fine Particulate Matter and High Humidity on Allergic Asthma: An Association with TRPV4\/MAPK Pathway Activation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-5307","authenticated-orcid":false,"given":"Ziyu","family":"Shu","sequence":"first","affiliation":[{"name":"Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-6299","authenticated-orcid":false,"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"Institute of Eastern-Himalaya Biodiversity Research, Dali University, Dali 671003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baizhan","family":"Li","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Ma","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Environmental Risks and Related Diseases Precision Control, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"Department of Pharmacy, Ezhou Central Hospital, Ezhou 436000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Guo","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China"},{"name":"School of Energy and Safety Engineering, Tianjin Chengjian University, Tianjin 300384, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenqiu","family":"Du","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3777-8428","authenticated-orcid":false,"given":"Fangxin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Earth Science and Engineering, Imperial College London, London SW7 2AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-7224","authenticated-orcid":false,"given":"Runming","family":"Yao","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China"},{"name":"School of the Built Environment, University of Reading, Reading RG6 6DB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12940-020-00681-z","article-title":"Synergistic Health Effects of Air Pollution, Temperature, and Pollen Exposure: A Systematic Review of Epidemiological Evidence","volume":"19","author":"Anenberg","year":"2020","journal-title":"Environ. 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