Extensive Phenotype of Human Inflammatory Monocyte-Derived Dendritic Cells.

Frédéric Coutant,Jean-Jacques Pin,Pierre Miossec

doi:10.3390/cells10071663

Abstract

Inflammatory monocyte-derived dendritic cells (Mo-DCs) have been described in several chronic inflammatory disorders, such as rheumatoid arthritis (RA), and are suspected to play a detrimental role by fueling inflammation and skewing adaptive immune responses. However, the characterization of their phenotype is still limited, as well as the comprehension of the factors that govern their differentiation. Here, we show that inflammatory Mo-DCs generated in vitro expressed a large and atypical panel of C-type lectin receptors, including isoforms of CD209 and CD206, CD303 and CD207, as well as intracellular proteins at their surfaces such as the lysosomal protein CD208. Combination of these markers allowed us to identify cells in the synovial fluid of RA patients with a close phenotype of inflammatory Mo-DCs generated in vitro. Finally, we found in coculture experiments that RA synoviocytes critically affected the phenotypic differentiation of monocytes into Mo-DCs, suggesting that the crosstalk between infiltrating monocytes and local mesenchymal cells is decisive for Mo-DCs generation.

Highlights

Since we performed a combination of double stainings, CD209-like/CD208, CD209-like/CD303, and CD209-like/CD123, we cannot rule out the possibility that several separate subsets of cells are present in the CD209-like+ cell population
A question still outstanding is the nature of the environmental factors that govern the differentiation of monocytes into monocyte-derived dendritic cells (Mo-dendritic cell (DC)), especially when monocytes infiltrate the synovial tissue of patients with rheumatoid arthritis (RA)
The present study shows that several C-type lectin receptors (CLRs) are expressed abundantly on the surface of Mo-DCs, such as CD209-like and CD206-like, the isoforms of CD209 and CD206, and to a lesser extent CD367, CD303, and CD207

Summary

Introduction

Academic Editors: Igal Ifergan and Alessandro Poggi. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Several dendritic cell (DC) subsets have been defined by their ontogeny, phenotype, and transcriptional profile, and all these subsets of DCs have been identified with altered phenotypes and functions in several chronic inflammatory/autoimmune disorders [1,2]. Blood DCs are categorized as CD303+ , CD304+ , CD123+ , plasmacytoid DCs (pDCs), and conventional DCs (cDCs), the latter being divided into two subsets, the CD1c+

Methods

Results

Conclusion