{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T05:44:45Z","timestamp":1791783885950,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["252102310141"],"award-info":[{"award-number":["252102310141"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Kcnn4 (KCa3.1) is a calcium\u2010activated potassium channel involved in cell volume regulation and immune cell function, but its role in salivary gland homeostasis remains poorly understood. In this study, we generated constitutive Kcnn4 knockout (\n                    <jats:italic>Kcnn<\/jats:italic>\n                    4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice to investigate the impact of Kcnn4 loss on salivary glands and systemic inflammation. Histological examination revealed that\n                    <jats:italic>Kcnn<\/jats:italic>\n                    4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had enlarged salivary glands with increased collagen deposition (fibrosis) but no major disorganization on H&amp;E staining. mRNA\u2010seq identified 473 differentially expressed genes (DEGs), with significant enrichment of T\u2010 and B\u2010cell\u2010related pathways. Immunofluorescence showed markedly increased infiltration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    , CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells into the salivary glands of knockout mice, yet local IgG levels were significantly decreased, which was confirmed by western blotting. Olink proteomic analysis of serum from\n                    <jats:italic>Kcnn<\/jats:italic>\n                    4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice revealed that among 43 targeted inflammatory proteins, 16 were significantly changed; 15 of these (including Il\u20106, Tnf, Cxcl1) were decreased, while only Csf1 was increased, indicating a broad systemic anti\u2010inflammatory shift. Collectively, these findings demonstrate that Kcnn4 deficiency induces salivary gland fibrosis, promotes T\/B cell infiltration, impairs local antibody production, and suppresses systemic inflammatory mediators, uncovering an unexpected role of Kcnn4 in integrating tissue remodeling and immune function in the salivary gland.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70412","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:46:58Z","timestamp":1791780418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Kcnn4<\/i>\n                    Knockout Induces Salivary Gland Fibrosis, Immune Cell Infiltration, and B\u2010Cell Dysfunction in Mice"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-8932","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, and People's Hospital of Henan University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7231-2070","authenticated-orcid":false,"given":"Siming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8495-4216","authenticated-orcid":false,"given":"Degui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Academy of Medical Science, Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2160-3043","authenticated-orcid":false,"given":"Cuiyun","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, and People's Hospital of Henan University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1570-7929","authenticated-orcid":false,"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute Zhengzhou University People's Hospital, Henan University People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7169-7226","authenticated-orcid":false,"given":"Hanlin","family":"Tao","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute Zhengzhou University People's Hospital, Henan University People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0318-0348","authenticated-orcid":false,"given":"Gongbo","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Eastern Hepatobiliary Surgery Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4508-5329","authenticated-orcid":false,"given":"Linna","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Hematology People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, School of Clinical Medicine, Henan University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3177-4194","authenticated-orcid":false,"given":"Shichao","family":"Duan","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute Zhengzhou University People's Hospital, Henan University People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1016\/j.jid.2018.05.034","article-title":"Long\u2010Term Increase of Kcnn4 Potassium Channel Surface Expression on B Cells in Pemphigus Patients After Rituximab Treatment","volume":"138","author":"Caillot F.","year":"2018","journal-title":"Journal of Investigative Dermatology"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"14644","DOI":"10.1038\/ncomms14644","article-title":"Potassium Channels Kv1.3 and KCa3.1 Cooperatively and Compensatorily Regulate Antigen\u2010Specific Memory T Cell Functions","volume":"8","author":"Chiang E. 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