Dendritic Cell Activating Receptor 1 (DCAR1) Associates With FcεRIγ and Is Expressed by Myeloid Cell Subsets in the Rat.

Michael R Daws,Régis Josien,Ana Lobato-Pascual,Sigbjørn Fossum,Britt Nakken,Erik Dissen

doi:10.3389/fimmu.2019.01060

Michael R Daws, Régis Josien + Show 4 more

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https://doi.org/10.3389/fimmu.2019.01060

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Abstract

Dendritic cell activating receptor-1 (DCAR1) is a cell-surface receptor encoded by the Antigen Presenting Lectin-like gene Complex (APLEC). We generated a mouse monoclonal antibody against rat DCAR1, and used this to characterize receptor expression and function. Rat DCAR1 was expressed on minor subsets of myeloid cells in lymphoid tissue, but was uniformly expressed at a high level by eosinophils, and at a low level by neutrophils. It was expressed by eosinophils in the peritoneal cavity and the lamina propria of the gut, and by subsets of macrophages or dendritic cells at these sites. Polarization of peritoneal macrophages showed that DCAR1 expression was absent on M1 macrophages, and increased on M2 macrophages. DCAR1 could be expressed as a homodimer and its associated with the activating adaptor protein FcεRIγ. This association allowed efficient phagocytosis of antibody-coated beads. Additionally, cross-linking of DCAR1 on the surface of rat eosinophils lead to production of reactive oxygen species. These data show that DCAR1 is an activating receptor. Its expression on M2 macrophages and eosinophils suggests that it may play a role in the immune response to parasites.

Highlights

We have previously identified a phylogenetically conserved cluster of structurally related receptor genes expressed primarily by myeloid cells [1]
Mice were immunized with rat Dendritic cell activating receptor-1 (DCAR1)-Fc fusion protein, and hybridomas screened for reactivity against transfected cells
We describe the development of a monoclonal antibody that reacts with rat DCAR1, and we use this antibody to characterize the receptor in the rat

Summary

Introduction

We have previously identified a phylogenetically conserved cluster of structurally related receptor genes expressed primarily by myeloid cells [1]. The complex, which we named the antigen-presenting cell lectin-like receptor gene complex (APLEC), encodes receptors belonging to group II C-type-lectins, i.e., type II surface receptors containing a single C-type lectin domain (CTLD) that retains the calcium-coordinating residues necessary for saccharide-binding [2]. The human APLEC contains five functional genes (DLEC, DCIR, Dectin 2, MCL, and Mincle), the mouse encodes nine and the rat seven genes presumed to be functional (DCAR1, MCL, Mincle and DCIR1,−2,−3, and−4). In contrast to the mouse APLEC, which encodes two DCAR family members (DCAR1 and−2, the latter called DCAR), the rat DCAR family consists of only one intact gene, Dcar, with Dcar reduced to incomplete gene fragments. There is no direct human ortholog of DCAR1, we have previously suggested that DLEC may fill this role [1]

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