Dendritic Cell immuno‐activating receptor 1 – Characterization of a novel member of the C‐type Lectin family

Abstract

C‐type lectins (CLEC) comprise a superfamily of cell surface proteins, whose multifunctional capacity has been shown to address both, innate and adaptive immune response. Here, we describe mDCAR1 a novel CLEC belonging to the recently defined murine dendritic cell (DC) immuno‐receptor (mDCIR)/DC immuno‐activating receptor (mDCAR) family.mDCAR1 expression was found to be restricted to mononuclear phagocytes in bone marrow. Extensive phenotypical characterization defined them as CCR2−CD62L−CX3CR1+Ly6C− cells, thereby belonging to the recently described ‘resident’ monocytes, which correspond to CD14+ CD16+ human monocytes. In contrast, the CCR2+CD62L+CX3CR1lowLy6C+ ‘inflammatory’ monocytes were mDCAR1−. Noteworthy, in thymus, mDCAR1 expression was found on CD11chighCD8alpha+CD205+CD11b−B220−BP‐1+ lymphoid‐related DC, which play an important role in central tolerance induction.With respect to the classical function of CLEC as antigen uptake receptors for pathogens and self‐proteins, mimicking the ligation of mDCAR1 by labeling with specific mAb shows the internalization of the mDCAR1/ligand complex. Crosslinking of mDCAR1 further initiates signal transduction resulting in tyrosine‐phosphorylation of proteins.The expression pattern of mDCAR1 and the evidence of a classical antigen‐uptake mechanism are first steps to uncover the role of this representative of the CLEC receptor family.