Academic Journal
Kcnn4 Knockout Induces Salivary Gland Fibrosis, Immune Cell Infiltration, and B-Cell Dysfunction in Mice.
| Title: | Kcnn4 Knockout Induces Salivary Gland Fibrosis, Immune Cell Infiltration, and B-Cell Dysfunction in Mice. |
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| Authors: | Zhang Y; Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, and People's Hospital of Henan University, Zhengzhou, China., Zheng S; Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China., Jiang D; Academy of Medical Science, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Cui C; Department of Transfusion Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, and People's Hospital of Henan University, Zhengzhou, China., Zhang X; Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China., Tao H; Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China., Fu G; Department of Oncology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China., Cheng L; Institute of Hematology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China., Duan S; Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China. |
| Source: | Chemical biology & drug design [Chem Biol Drug Des] 2026 Oct; Vol. 108 (4), pp. e70412. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262549 Publication Model: Print Cited Medium: Internet ISSN: 1747-0285 (Electronic) Linking ISSN: 17470277 NLM ISO Abbreviation: Chem Biol Drug Des Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford : Wiley-Blackwell, 2006- |
| MeSH Terms: | Intermediate-Conductance Calcium-Activated Potassium Channels*/genetics , Intermediate-Conductance Calcium-Activated Potassium Channels*/deficiency , Intermediate-Conductance Calcium-Activated Potassium Channels*/metabolism , B-Lymphocytes*/immunology , B-Lymphocytes*/metabolism , B-Lymphocytes*/cytology , Salivary Glands*/pathology , Salivary Glands*/metabolism , Salivary Glands*/immunology, Animals ; Mice, Knockout ; Mice ; Fibrosis ; Mice, Inbred C57BL |
| Abstract: | Kcnn4 (KCa3.1) is a calcium-activated 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 (Kcnn4-/-) mice to investigate the impact of Kcnn4 loss on salivary glands and systemic inflammation. Histological examination revealed that Kcnn4-/- mice had enlarged salivary glands with increased collagen deposition (fibrosis) but no major disorganization on H&E staining. mRNA-seq identified 473 differentially expressed genes (DEGs), with significant enrichment of T- and B-cell-related pathways. Immunofluorescence showed markedly increased infiltration of CD4+, CD8+ T cells and CD19+ 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 Kcnn4-/- mice revealed that among 43 targeted inflammatory proteins, 16 were significantly changed; 15 of these (including Il-6, Tnf, Cxcl1) were decreased, while only Csf1 was increased, indicating a broad systemic anti-inflammatory 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. (© 2026 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.) |
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| Grant Information: | LHGJ20250094 Henan Medical Science and Technology Research Project; 252102310141 Henan Science and Technology Research Project |
| Contributed Indexing: | Keywords: IgG deficiency; Kcnn4 (KCa3.1); fibrosis; inflammatory proteomics; lymphocyte infiltration; salivary gland |
| Substance Nomenclature: | 0 (Intermediate-Conductance Calcium-Activated Potassium Channels) 0 (Kcnn4 protein, mouse) |
| Entry Date(s): | Date Created: 20261012 Date Completed: 20261012 Latest Revision: 20261014 |
| Update Code: | 20261014 |
| PubMed Central ID: | PMC13655356 |
| DOI: | 10.1111/cbdd.70412 |
| PMID: | 42860661 |
| Database: | MEDLINE |
| ISSN: | 1747-0285 |
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| DOI: | 10.1111/cbdd.70412 |