{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:33:32Z","timestamp":1782311612112,"version":"3.54.5"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Severe COVID-19 is characterized by cytokine storm, an excessive production of proinflammatory cytokines that contributes to acute lung damage and death. Dexamethasone is routinely used to treat severe COVID-19 and has been shown to reduce patient mortality. However, the mechanisms underlying the beneficial effects of dexamethasone are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild disease, and patients with severe COVID-19 with and without dexamethasone treatment. We then treated healthy donor PBMCs in vitro with dexamethasone and investigated the effects of dexamethasone treatment ion channel abundance (by RT-qPCR and flow cytometry) and function (by electrophysiology, Ca2+ influx measurements and cytokine release) in T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that dexamethasone treatment in severe COVID-19 inhibited pro-inflammatory and immune exhaustion pathways, circulating cytotoxic and Th1 cells, interferon (IFN) signaling, genes involved in cytokine storm, and Ca<jats:sup>2+<\/jats:sup> signaling. Ca<jats:sup>2+<\/jats:sup> influx is regulated by Kv1.3 potassium channels, but their role in COVID-19 pathogenesis remains elusive. Kv1.3 mRNA was increased in PBMCs of severe COVID-19 patients, and was significantly reduced in the dexamethasone-treated group. In agreement with these findings, in vitro treatment of healthy donor PBMCs with dexamethasone reduced Kv1.3 abundance in T cells and CD56dimNK cells. Furthermore, functional studies showed that dexamethasone treatment significantly reduced Kv1.3 activity, Ca2+ influx and IFN-g production in T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1143350","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T06:04:14Z","timestamp":1679637854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19"],"prefix":"10.3389","volume":"14","author":[{"given":"Ameet 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