{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Elizondo DM"],"funding":["U.S. Department of Defense","National Institutes of Health","NIGMS NIH HHS","National Science Foundation"],"pagination":["855-864"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6608068"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["100(5)"],"pubmed_abstract":["ADAM23 is a member of the brain macrophage-derived chemokine family. Structural homology of ADAM proteins suggests their function as integrin receptors. Previous studies have linked ADAM23 as a dominant contributor to brain development and cancer metastasis. The present studies now show that ADAM23 expression on DCs partially governs antigen-presentation capacities to responder CD4<sup>+</sup> T cells. With the use of RNAi approaches, knockdown of ADAM23 in murine BMDCs resulted in impaired T cell activation, proliferation, and cytokine production. Knockdown did not alter the maturation profile of DCs (i.e., costimulatory molecule expression or production of proinflammatory cytokines) but markedly impaired cognate T cell responses. There was a significant decrease in antigen-specific clonal expansion coupled with a global decrease in Th cytokine production. Impaired early activation and proliferation did not alter/skew the balance of Th polarization but significantly depressed total levels of IL-2, IFN-γ, IL-4, and IL-17 cytokine production in CD4<sup>+</sup> T cells primed by ADAM23 knockdown versus control DCs. Finally, neutralizing antibodies targeting the α(v)β(3) integrin receptors resulted in similar phenotypes of impaired CD4<sup>+</sup> T cell responses. Taken together, these studies show a novel role of ADAM23 in governing DC antigen presentation to cognate CD4<sup>+</sup> T cells."],"journal":["Journal of leukocyte biology"],"pubmed_title":["Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor."],"pmcid":["PMC6608068"],"funding_grant_id":["#W911NF‐14‐1‐0123","SC2 GM103741","#1SC2GM103741","#1428768"],"pubmed_authors":["Lipscomb MW","Zariwala AM","Elizondo DM","Andargie TE","Marshall KM"],"additional_accession":[]},"is_claimable":false,"name":"Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor.","description":"ADAM23 is a member of the brain macrophage-derived chemokine family. Structural homology of ADAM proteins suggests their function as integrin receptors. Previous studies have linked ADAM23 as a dominant contributor to brain development and cancer metastasis. The present studies now show that ADAM23 expression on DCs partially governs antigen-presentation capacities to responder CD4<sup>+</sup> T cells. With the use of RNAi approaches, knockdown of ADAM23 in murine BMDCs resulted in impaired T cell activation, proliferation, and cytokine production. Knockdown did not alter the maturation profile of DCs (i.e., costimulatory molecule expression or production of proinflammatory cytokines) but markedly impaired cognate T cell responses. There was a significant decrease in antigen-specific clonal expansion coupled with a global decrease in Th cytokine production. Impaired early activation and proliferation did not alter/skew the balance of Th polarization but significantly depressed total levels of IL-2, IFN-γ, IL-4, and IL-17 cytokine production in CD4<sup>+</sup> T cells primed by ADAM23 knockdown versus control DCs. Finally, neutralizing antibodies targeting the α(v)β(3) integrin receptors resulted in similar phenotypes of impaired CD4<sup>+</sup> T cell responses. Taken together, these studies show a novel role of ADAM23 in governing DC antigen presentation to cognate CD4<sup>+</sup> T cells.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2025-04-22T20:34:15.514Z","creation":"2019-07-25T07:03:23Z"},"accession":"S-EPMC6608068","cross_references":{"pubmed":["27317750"],"doi":["10.1189/jlb.2hi1115-525r","10.1189/jlb.2HI1115-525R"]}}