1 research outputs found
Characterisation of the C-type lectin receptor CLEC-2: expression, ligands and functions
Myeloid cells express a plethora of C-type lectin receptors (CLR) that can
regulate inflammatory responses. Dectin-1 belongs to a sub-family of CLRs that
possesses an extracellular C-type lectin domain (CTLD) and a single YxxL
intracellular motif (hemITAM) that allows signalling via Syk kinase and induction
of downstream functions. Based on consensus sequences for the CTLD and
hemITAM, we identified CLEC-2 as a dectin-1-like receptor. CLEC-2 was
previously characterised as a Syk-coupled platelet receptor able to induce
platelet aggregation when targeted by the snake venom rhodocytin and by cells
expressing the endogenous protein podoplanin. I generated monoclonal
antibodies against mouse CLEC-2 and found that CLEC-2 is also expressed on
lymphoid and myeloid cells, including dendritic cells (DC). Notably, treatment
with LPS increases CLEC-2 expression by myeloid cells and synergises with
CLEC-2 signaling to induce increased secretion of IL-10 but not IL-12. This
increased IL-10 production is also observed in the serum of mice administered
with anti-CLEC-2 mAb and LPS, and is dependent on the presence of
macrophages and DCs. Furthermore, I generated a CLEC-2 conditional KO
mouse line that will provide a tool to study CLEC-2 function in myeloid cells in
vivo. Collectively, these data indicate that CLEC-2 expression is not restricted
to platelets and that it plays a role on the vascular development and modulation
of TLR responses