Oncotarget

Research Papers: Immunology:

This article has been corrected. Correction in: Oncotarget. 2016; 7(40):66323.

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

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

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Oncotarget. 2016; 7:161-175. https://doi.org/10.18632/oncotarget.6660

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Abstract

Alessandra Micheletti1, Giulia Finotti1, Federica Calzetti1, Silvia Lonardi2, Elisa Zoratti3, Mattia Bugatti2, Stefania Stefini4, William Vermi2,5 and Marco A. Cassatella1

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+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.


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