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slan/M-DC8+ cells constitute a distinct subset of dendritic cells in human tonsils

2015; Impact Journals LLC; Volume: 7; Issue: 1 Linguagem: Inglês

10.18632/oncotarget.6660

1949-2553

Alessandra Micheletti, Giulia Finotti, Federica Calzetti, Silvia Lonardi, Elisa Zoratti, Mattia Bugatti, Stefania Stefini, William Vermi, Marco A. Cassatella,

T-cell and B-cell Immunology

// Alessandra Micheletti 1 , Giulia Finotti 1 , Federica Calzetti 1 , Silvia Lonardi 2 , Elisa Zoratti 3 , Mattia Bugatti 2 , Stefania Stefini 4 , William Vermi 2,5 and Marco A. Cassatella 1 1 Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy 2 Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy 3 Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy 4 Unit of Pediatric Otorhinolaryngology, Spedali Civili di Brescia, Brescia, Italy 5 Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA Correspondence to: Marco A. Cassatella, email: // Keywords : slan/M-DC8+ cells, dendritic cells, monocytes, tonsil, differentiation, Immunology and Microbiology Section, Immune response, Immunity Received : September 10, 2015 Accepted : November 22, 2015 Published : December 18, 2015 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 + CD11b dim/neg CD16 dim/neg CX3CR1 dim/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.