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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:568240 |
| Date | January 2011 |
| Creators | Souto Maior Mourão Sá, D. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1302407/ |
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