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.
Highlights
Dendritic cells (DCs) represent a heterogeneous population of myeloid cells that are characterized by a very efficient capacity to present antigens to T cells
We have performed an extensive phenotypic and functional characterization of slan/MDC8+ cells in human tonsils, which proves that these cells represent a unique CD11c+HLADR+CD14+CD11bdim/negCD16dim/negCX3CR1dim/neg population of dendritic cells (DCs), different from other classical CD1c+ and CD141+ myeloid DCs (mDCs) or CD14+CD11b+ monocytes/ macrophages
Our data demonstrate that tonsil slan/M-DC8+ DCs differ from their blood counterparts, characterized by a CD11c+HLA-DR+CD14dimCD11bdim CD16brightCX3CR1bright phenotype, suggesting that blood slan/M-DC8+ cells undergo a DC differentiation process once migrated into tonsils
Summary
Dendritic cells (DCs) represent a heterogeneous population of myeloid cells that are characterized by a very efficient capacity to present antigens to T cells. The plasmacytoid DCs (pDCs), that are specialized in type I interferon production [3], and the conventional myeloid DCs (mDCs), that include the CD1c+(BDCA1+) DCs and the CD141+(BDCA3+) DCs, the latter ones being skilled at antigen cross-presentation to CD8+ T cells [4]. All these DC populations have been found in secondary lymphoid organs, including tonsils, spleen and lymph nodes [5,6,7]. Our data suggest that blood slan/M-DC8+ cells contribute to replenish such slan/M-DC8+ DC pool in tonsils, uncovering new information on plasticity by blood slan/ M-DC8+ cells and their ultimate commitment within tissue microenvironments
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