Calhm6 Governs Macrophage Polarization Through Chp1-Camk4-Creb1 Axis and Ectosomal Delivery in Inflammatory Responses.

ABSTRACT: Macrophage plasticity, critical for immune response, is often dysregulated in various infectious and inflammatory diseases. While ion channels have been implicated in immune cell modulation, how they influence macrophage polarization remains poorly understood. Here, it is demonstrated that ectosomes carrying the ion channel Calhm6 effectively suppress severe inflammation triggered by LPS. These Calhm6-bearing ectosomes, secreted by macrophages, facilitate M2-like polarization, elicit an anti-inflammatory response, and foster immune tolerance. Conversely, Calhm6 deficiency leads to suppressed Creb1 activity, which in turn augments M1-like macrophage polarization, enhancing bactericidal activity and the secretion of pro-inflammatory cytokines. Mechanistically, Chp1 serves as a scaffold prote

SUBMITTER: Xin Y 

PROVIDER: S-EPMC12766987 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature