Document Detail


CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses.
MedLine Citation:
PMID:  21728173     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Myeloid cells express a plethora of C-type lectin receptors (CLR) 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 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 toll-like receptor signaling and inflammatory responses.
Authors:
Diego Mourão-Sá; Matthew J Robinson; Santiago Zelenay; David Sancho; Probir Chakravarty; Rasmus Larsen; Maud Plantinga; Nico Van Rooijen; Miguel P Soares; Bart Lambrecht; Caetano Reis E Sousa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-4
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Immunobiology Laboratory, Cancer Research UK, London Research Institute, WC2A 3LY London, United Kingdom.
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