Featured Publications

In this study, Cheng et al. report that the proton-activated chloride (PAC) channel works as a phagosome “brake”, limiting acidification and protease activation in macrophages during bacterial infection. Deletion of PAC enhances macrophage bactericidal activities and prevents septicemia in mice by promoting STING signaling and gasdermin D secretion. –HYC/SF

In this study, Li et al. report that that serotonin transporter (SERT) inhibits CD8 T cell antitumor immunity by depleting intratumoral serotonin. SERT-blocking SSRI antidepressants enhance CD8 T cell function and synergize with anti-PD-1 therapy, suggesting SSRIs as potential cancer immunotherapeutics. –HYC/ZQ

Zhong et al. report that store-operated Ca2+ entry (SOCE) activated by STIM1 and mediated by ORAI channels is required for the differentiation of Th1 cells, which are crucial for immunity against intracellular pathogens. SOCE synergizes with IFN-γ induced STAT1 signaling to promote expression of the Th1 transcription factor T-bet. Loss of STIM1 impairs Th1 differentiation, particularly when the cytokine IL-12 is absent. As many viruses do not induce IL-12 production and IL-12 production is low in infants, these findings highlight the importance of SOCE in early life immune responses. –HYC/SF

This study shows that the Kir6.1 subunit of a type of ATP-sensitive potassium (KATP) channels is highly expressed in murine NK cells and that NK cells express a current sensitive to a Kir6.1 blocker. NK cell specific knockout of Kcnj8 (encoding Kir6.1) attenuates NK cell maturation, but has no effect on NK cell degranulation, IFN-γ release and tumor cell killing. –WAC

Doyle et al. demonstrate that TRPM7 ion channel activity is essential for acidification of virus-containing endosomes by providing a cationic countercurrent that enables sustained V-ATPase proton pumping, with loss or pharmacological inhibition of TRPM7 preventing infection by pH-dependent enveloped viruses (Lassa, LCMV, Ebola, SARS-CoV-2, influenza) but not pH-independent viruses (VSV, rabies). This positions TRPM7 as a potential broad-spectrum antiviral target, as its channel activity specifically regulates the acidification of virus-laden endosomes without affecting general endosomal function, and pharmacological inhibition protected mice from influenza infection in vivo. –BD