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Dendritic cells (DCs) are essential for the development of asthma via presenting allergens, causing T-helper cell type 2 (Th2) skewing and eosinophil inflammation. Recent studies have revealed that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and psoriasis. However, no study has addressed the role of CD109 in asthma. This study sought to address the role of CD109 on DCs in the development of AHR and allergic inflammation. CD109-deficient mice (CD109\u2212\/\u2212) were sensitized with house dust mite or ovalbumin and compared with wild-type mice for induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR and eosinophilic inflammation together with lower Th2 cytokine expression compared with wild-type mice. Interestingly, CD109 expression was induced in lung conventional DC2s (cDC2s), but not lung cDC1s, upon allergic challenge. Lung cDC2s from CD109\u2212\/\u2212 mice had a poor ability to induce cytokine production in ex vivo DC\u2013T cell cocultures with high expression of RUNX3 (runt-related transcription factor 3), resulting in suppression of Th2 differentiation. Adoptive transfer of bone marrow\u2013derived CD109\u2212\/\u2212 DCs loaded with house dust mite failed to develop AHR and eosinophilic inflammation. Finally, administration of monoclonal anti-CD109 antibody reduced airway eosinophils and significantly decreased AHR. Our results suggest the involvement of CD109 in asthma pathogenesis. CD109 is a novel therapeutic target for asthma.<\/jats:p>","DOI":"10.1165\/rcmb.2022-0109oc","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T15:53:10Z","timestamp":1665417190000},"page":"201-212","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":22,"title":["CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation"],"prefix":"10.1093","volume":"68","author":[{"given":"Yuya","family":"Aono","sequence":"first","affiliation":[{"name":"Second Division, Department of Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-9791","authenticated-orcid":false,"given":"Yuzo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Second Division, Department of Internal Medicine, 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