title: CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses.
abstract: 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.
authors: Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
authors: Diego
authors: D
authors: Mourão-Sá
authors: Matthew J
authors: MJ
authors: Robinson
authors: Santiago
authors: S
authors: Zelenay
authors: David
authors: D
authors: Sancho
authors: Probir
authors: P
authors: Chakravarty
authors: Rasmus
authors: R
authors: Larsen
authors: Maud
authors: M
authors: Plantinga
authors: Nico
authors: N
authors: Van Rooijen
authors: Miguel P
authors: MP
authors: Soares
authors: Bart
authors: B
authors: Lambrecht
authors: Caetano
authors: C
authors: Reis e Sousa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001792:Blood Platelets; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: D000911:Antibodies, Monoclonal; C529518:CLEC-2 protein, mouse; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; D051193:Toll-Like Receptors; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D015232:Dinoprostone; D002118:Calcium