<i>Kcnn4</i> Knockout Induces Salivary Gland Fibrosis, Immune Cell Infiltration, and B‐Cell Dysfunction in Mice

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 ( Kcnn 4 ^−/− ) mice to investigate the impact of Kcnn4 loss on salivary glands and systemic inflammation. Histological examination revealed that Kcnn 4 ^−/− 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 Kcnn 4 ^−/− 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.