title: slanDCs/M-DC8+ cells constitute a distinct subset of dendritic cells in human tonsils [corrected].
abstract: Human blood dendritic cells (DCs) include three main distinct subsets, namely the CD1c+ and CD141+ myeloid DCs (mDCs) and the CD303+ plasmacytoid DCs (pDCs). More recently, a population of slan/M-DC8+ cells, also known as "slanDCs", has been described in blood and detected even in inflamed secondary lymphoid organs and non-lymphoid tissues. Nevertheless, hallmarks of slan/M-DC8+ cells in tissues are poorly defined. Herein, we report a detailed characterization of the phenotype and function of slan/M-DC8+ cells present in human tonsils. We found that tonsil slan/M-DC8+ cells represent a unique DC cell population, distinct from their circulating counterpart and also from all other tonsil DC and monocyte/macrophage subsets. Phenotypically, slan/M-DC8+ cells in tonsils display a CD11c+HLA-DR+CD14+CD11bdim/negCD16dim/negCX3CR1dim/neg marker repertoire, while functionally they exhibit an efficient antigen presentation capacity and a constitutive secretion of TNFα. Notably, such DC phenotype and functions are substantially reproduced by culturing blood slan/M-DC8+ cells in tonsil-derived conditioned medium (TDCM), further supporting the hypothesis of a full DC-like differentiation program occurring within the tonsil microenvironment. Taken together, our data suggest that blood slan/M-DC8+ cells are immediate precursors of a previously unrecognizedcompetent DC subset in tonsils, and pave the way for further characterization of slan/M-DC8+ cells in other tissues.
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micheletti
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Finotti
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Calzetti
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bugatti
authors.affiliation: Unit of Pediatric Otorhinolaryngology, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Stefini
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.|Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D039521:CD11c Antigen; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D019707:Receptors, Chemokine; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha
keywords: Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; differentiation; monocytes; slan/M-DC8+ cells; tonsil