CD40-CD40L cross-talk drives fascin expression in dendritic cells for efficient antigen presentation to CD4+ T cells

Diana M. Elizondo, Temesgen E. Andargie, Dineeta S. Kubhar, Ayele Gugssa, Michael W. Lipscomb

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Fascin is an actin-bundling protein that, among immune cells, is restricted to expression in dendritic cells (DCs). Previous reports have suggested that fascin plays an important role in governing DC antigen presentation to CD4+ T cells. However, no report has clearly linked the receptor-ligand engagement that can direct downstream regulation of fascin expression. In this study, bone marrow-derived DCs from wild-type versus CD40-knockout C57BL/6 mice were used to elucidate the mechanisms of fascin expression and activity upon CD40-CD40 ligand (CD40L) engagement. These investigations now show that CD40 engagement governs fascin expression in DCs to promote CD4+ T-cell cytokine production. Absence of CD40 signaling resulted in diminished fascin expression in DCs and was associated with impaired CD4+ T-cell responses. Furthermore, the study found that loss of CD40-CD40L engagement resulted in reduced DC-T-cell contacts. Rescue by ectopic fascin expression in CD40-deficient DCs was able to re-establish sustained contacts with T cells and restore cytokine production. Taken together, these results show that cross-talk through CD40-CD40L signaling drives elevated fascin expression in DCs to support acquisition of full T-cell responses.

Original languageEnglish (US)
Article numberdxx013
Pages (from-to)121-131
Number of pages11
JournalInternational Immunology
Volume29
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Lynda Chin for providing the pLenti6/V5-DEST-FASCIN vector. The authors would also like to thank Franklin Ampy and Winston Anderson for assistance in statistical analyses and editing of the manuscript. This work was supported by the National Institutes of Health (grant number SC2GM103741 to M.W.L.); Department of Defense (grant number W911NF-14-1-0123 to M.W.L.); National Sciences Foundation (grant number DBI-1428768 to M.W.L. and W. Anderson).

Publisher Copyright:
© The Japanese Society for Immunology 2017. All rights reserved.

Keywords

  • Actin bundling
  • Co-receptor
  • Co-stimulation
  • Cytoskeleton
  • Immune synapse

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