title: CD40-CD40L cross-talk drives fascin expression in dendritic cells for efficient antigen presentation to CD4+ T cells.
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.
authors.affiliation: Biology Department, Howard University, 415 College Street NW, Washington, DC 20059, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Elizondo
authors.affiliation: Biology Department, Howard University, 415 College Street NW, Washington, DC 20059, USA.
authors.forename: Temesgen E
authors.initials: TE
authors.lastname: Andargie
authors.affiliation: Biology Department, Howard University, 415 College Street NW, Washington, DC 20059, USA.
authors.forename: Dineeta S
authors.initials: DS
authors.lastname: Kubhar
authors.affiliation: Biology Department, Howard University, 415 College Street NW, Washington, DC 20059, USA.
authors.forename: Ayele
authors.initials: A
authors.lastname: Gugssa
authors.affiliation: Biology Department, Howard University, 415 College Street NW, Washington, DC 20059, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lipscomb
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000172:deficiency / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin; D023201:CD40 Ligand
keywords: actin bundling; co-receptor; co-stimulation; cytoskeleton; immune synapse