The expression of mouse CLEC‐2 on leucocyte subsets varies according to their anatomical location and inflammatory state

Abstract

Expression of mouse C‐type lectin‐like receptor 2 (CLEC‐2) has been reported on circulating CD11bhigh Gr‐1high myeloid cells and dendritic cells (DCs) under basal conditions, as well as on a variety of leucocyte subsets following inflammatory stimuli or in vitro cell culture. However, previous studies assessing CLEC‐2 expression failed to use CLEC‐2‐deficient mice as negative controls and instead relied heavily on single antibody clones. Here, we generated CLEC‐2‐deficient adult mice using two independent approaches and employed two anti‐mouse CLEC‐2 antibody clones to investigate surface expression on hematopoietic cells from peripheral blood and secondary lymphoid organs. We rule out constitutive CLEC‐2 expression on resting DCs and show that CLEC‐2 is upregulated in response to LPS‐induced systemic inflammation in a small subset of activated DCs isolated from the mesenteric lymph nodes but not the spleen. Moreover, we demonstrate for the first time that peripheral blood B lymphocytes present exogenously derived CLEC‐2 and suggest that both circulating B lymphocytes and CD11bhigh Gr‐1high myeloid cells lose CLEC‐2 following entry into secondary lymphoid organs. These results have significant implications for our understanding of CLEC‐2 physiological functions

Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis

“…Neutrophils have been reported to express CLEC-2 in 1 study 34 but not another. 25 The finding that platelet-specific knockout mice have decreased thrombosis suggests a predominant role of CLEC-2 on platelets in DVT initiation. The reason for different median thrombus size in the WT (Cre 2 littermates) groups of BLOOD, 6 APRIL 2017 x VOLUME 129, NUMBER 14 CLEC-2 PROMOTES DVT 2015…”

HemITAM: A single tyrosine motif that packs a punch

“…The latter study also reported accumulation of Clec-2 on myeloid cells and NK cells upon lipopolysaccharide (LPS) challenge together with a de novo appearance of Clec-2 on B cells (44). A more recent report, however, attributed Clec-2 on mouse B cells to the acquisition from exogenous sources, for example, by trogocytosis, and showed that Clec-2 on mouse myeloid cells is lost during the entrance of these cells into secondary lymphoid organs (45). The function of CLEC-2 on platelets is well defined as stimulating platelet activation and aggregation (10,24,41).…”

Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes

“…10 Podoplanin is the only described endogenous ligand of the C-type lectin-like receptor 2 (CLEC-2), 11 which is expressed by platelets 12 and activated dendritic cells (DCs). [13][14][15] CLEC-2 signaling is involved in platelet activation, 12 DC motility 15 and in the maintenance of vascular integrity, 16 LN structure and development. 17 Podoplanin global knockout mice die shortly after birth because of a failure to inflate their lungs.…”