biostudies-literatureElizondo DMU.S. Department of DefenseNational Institutes of HealthNIGMS NIH HHSNational Science Foundation855-864https://www.ebi.ac.uk/biostudies/studies/S-EPMC6608068biostudies-literatureUnknown100(5)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⁺ 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⁺ 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⁺ T cell responses. Taken together, these studies show a novel role of ADAM23 in governing DC antigen presentation to cognate CD4⁺ T cells.Journal of leukocyte biologyDendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor.PMC6608068#W911NF‐14‐1‐0123SC2 GM103741#1SC2GM103741#1428768Lipscomb MWZariwala AMElizondo DMAndargie TEMarshall KMfalseDendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor.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⁺ 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⁺ 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⁺ T cell responses. Taken together, these studies show a novel role of ADAM23 in governing DC antigen presentation to cognate CD4⁺ T cells.2016-01-01T00:00:00Z2016 Nov2025-04-22T20:34:15.514Z2019-07-25T07:03:23ZS-EPMC66080682731775010.1189/jlb.2hi1115-525r10.1189/jlb.2HI1115-525R