title: Bright expression of CD91 identifies highly activated human dendritic cells that can be expanded by defensins.
abstract: CD91 is a scavenger receptor expressed by different immune cells and its ligands defensins have been demonstrated to contribute to immune responses against infections and tumours. We previously demonstrated that CD91 is expressed on human monocyte-derived dendritic cells (moDCs) and that human defensins stimulate in vitro the activation of these cells. In this study, we observed that CD91 is expressed at different levels on two distinct moDC subsets: CD91(dim) and CD91(bright) moDCs. Although CD91(bright) moDCs represented a small proportion of total moDCs, this subset showed higher levels of activation and maturation markers compared with CD91(dim) moDCs. The frequency of CD91(bright) moDCs increased by ~ 50% after in vitro stimulation with recombinant human neutrophil peptide-1 (rHNP-1) and recombinant human β defensin-1 (rHBD-1), while lipopolysaccharide (LPS) stimulation decreased it by ~ 35%. Both defensins up-regulated moDC expression of CD80, CD40, CD83 and HLA-DR, although to a lower extent compared with LPS. Notably, upon culture with rHNP-1 and rHBD-1, CD91(bright) moDCs maintained their higher activation/maturation status, whereas this was lost upon culture with LPS. Our findings suggest that defensins promote the differentiation into activated CD91(bright) DCs and may encourage the exploitation of the CD91/defensins axis as a novel therapeutic strategy to potentiate antimicrobial and anti-tumour immune response.
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy; Laboratory of Clinical and Experimental Immunology, Humanitas Clinical and Research Centre, Rozzano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cappelletti
authors.forename: Pietro
authors.initials: P
authors.lastname: Presicce
authors.forename: Francesca
authors.initials: F
authors.lastname: Calcaterra
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Bella
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation; D023084:alpha-Defensins / Q000494:pharmacology*; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: C406407:DEFB1 protein, human; C475476:LRP1 protein, human; D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011994:Recombinant Proteins; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1
keywords: CD91; defensins; dendritic cells; human neutrophil peptide-1; human β defensin-1