Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(V)β(3) integrin receptor

D. M. Elizondo, T. E. Andargie, K. M. Marshall, A. M. Zariwala, M. W. Lipscomb

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)855-864
Number of pages10
JournalJournal of Leukocyte Biology
Issue number5
StatePublished - Nov 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded, in part, by the U.S. National Institutes of Health (Grant #1SC2GM103741), Department of Defense (Grant #W911NF-14-1-0123), and National Science FoundationNSF(Grant #1428768). The authors thank Dr. Franklin Ampy for assistance in statistical analyses and Dr. Winston Anderson for revisions and edits of the manuscript.

Publisher Copyright:
© Society for Leukocyte Biology.


  • Adhesion
  • Antigen presentation
  • Costimulation
  • Cytoskeleton
  • Disintegrin


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