Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the ?(v)?(3) integrin receptor.

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⁺ 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-?, IL-4, and IL-17 cytokine production in CD4⁺ T cells primed by ADAM23 knockdown versus control DCs. Finally, neutralizing antibodies targeting the ?(v)?(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.

SUBMITTER: Elizondo DM 

PROVIDER: S-EPMC6608068 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature