{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chimote AA"],"funding":["NCI NIH HHS","NIH","NIAMS NIH HHS"],"pagination":["86-93"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4830342"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["69"],"pubmed_abstract":["Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro-inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naïve. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials."],"journal":["Journal of autoimmunity"],"pubmed_title":["Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype."],"pmcid":["PMC4830342"],"funding_grant_id":["P30 AR047363","R01 CA095286","R21AR060966","R01CA095286","P30 AR070549","R21 AR060966"],"pubmed_authors":["Conforti L","Yun Y","Harley JB","Hajdu P","Chimote AA","Kottyan LC"],"additional_accession":[]},"is_claimable":false,"name":"Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype.","description":"Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro-inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naïve. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 May","modification":"2025-04-18T16:20:53.29Z","creation":"2019-03-27T03:11:55Z"},"accession":"S-EPMC4830342","cross_references":{"pubmed":["26994905"],"doi":["10.1016/j.jaut.2016.03.004"]}}