CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses

Eur J Immunol. 2011 Oct;41(10):3040-53. doi: 10.1002/eji.201141641. Epub 2011 Aug 17.


Myeloid cells express a plethora of C-type lectin receptors (CLRs) that can regulate immune responses. CLEC-2 belongs to the Dectin-1 sub-family of CLRs that possess an extracellular C-type lectin-like domain and a single intracellular hemITAM motif. CLEC-2 is highly expressed on mouse and human platelets where it signals via Syk to promote aggregation. We generated a monoclonal antibody (mAb) against mouse CLEC-2 and found that CLEC-2 is additionally widely expressed on leukocytes and that its expression is upregulated during inflammation. MAb-mediated crosslinking of CLEC-2 leads to hemITAM-dependent signaling via Syk, Ca(2+) and NFAT and, in myeloid cells, modulates the effect of toll-like receptor (TLR) agonists to selectively potentiate production of IL-10. A macrophage/dendritic cell-dependent increase in IL-10 is also observed in mice given anti-CLEC-2 mAb together with LPS. Collectively, these data indicate that CLEC-2 is expressed in myeloid cells and acts as a Syk-coupled CLR able to modulate TLR signaling and inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Blood Platelets
  • Calcium / metabolism
  • Cell Line
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dinoprostone / metabolism
  • Inflammation
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-10 / biosynthesis
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Lipopolysaccharides / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • NFATC Transcription Factors / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Syk Kinase
  • Toll-Like Receptors / agonists


  • Antibodies, Monoclonal
  • CLEC-2 protein, mouse
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Lipopolysaccharides
  • NFATC Transcription Factors
  • Toll-Like Receptors
  • Interleukin-10
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • Dinoprostone
  • Calcium