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Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early Streptococcus pneumoniae (SP) infection. However, its function remains largely unexplored. Here, we aimed to clarify the function of Sectm1a during serotype 3 pneumococcal pneumonia primarily using an in vivo mouse model. Our findings showed that Type I IFNs directly induced Sectm1a expression in AECs. Sectm1a depletion in an in vivo mouse model improved survival rate and enhanced the clearance of intrapulmonary bacterial burden at an early stage of SP infection. Correspondingly, Sectm1a depletion increased the count of intrapulmonary \u03b3\u03b4T cells, promoted IL-17A production by these cells, and enhanced intrapulmonary neutrophil responses against SP. Notably, IL-17A production in isolated lung \u03b3\u03b4T cells was directly suppressed by Sectm1a ex vivo. Furthermore, Sectm1a depletion altered the migration and activation markers of \u03b3\u03b4T cells in vivo, indicating that the AEC-derived Sectm1a is associated with the phenotypes of \u03b3\u03b4T cells. These findings suggest that Type I IFNs may play an important role through AEC-derived Sectm1a in this model, and Sectm1a signaling modulates excessive neutrophil inflammation and influences bacterial clearance by directly altering \u03b3\u03b4T cell functions during pneumococcal pneumonia. In summary, this study demonstrates that the Type I IFN\u2013Sectm1a pathway could be a potential target to modify the acute response to bacterial pneumonia.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0276oc","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T17:17:49Z","timestamp":1734628669000},"page":"60-72","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["Sectm1a Depletion Promotes Neutrophil Recruitment during Pneumococcal Pneumonia"],"prefix":"10.1093","volume":"73","author":[{"given":"Hiromu","family":"Tanaka","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kamata","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Azekawa","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kaji","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genta","family":"Nagao","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyasu","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Health Center, Keio University, Tokyo, 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