The C-type lectin receptor CLECSF8 (CLEC4D) is expressed by myeloid cells and triggers cellular activation through syk kinase

Lisa M. Graham, Vandana Gupta, Georgia Schafer, Delyth M. Reid, Matti Kimberg, Kevin M. Dennehy, William G. Hornsell, Reto Guler, Maria A. Campanero-Rhodes, Angelina S. Palma, Ten Feizi, Stella K. Kim, Peter Sobieszczuk, Janet A. Willment, Gordon D. Brown

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

CLECSF8 is a poorly characterized member of the "Dectin-2 cluster" of C-type lectin receptors and was originally thought to be expressed exclusively by macrophages. We show here that CLECSF8 is primarily expressed by peripheral blood neutrophils and monocytes and weakly by several subsets of peripheral blood dendritic cells. However, expression of this receptor is lost upon in vitro differentiation of monocytes into dendritic cells or macrophages. Like the other members of the Dectin-2 family, which require association of their transmembrane domains with signaling adaptors for surface expression, CLECSF8 is retained intracellularly when expressed in non-myeloid cells. However, we demonstrate that CLECSF8 does not associate with any known signaling adaptor molecule, including DAP10, DAP12, or the FcRγ chain, and we found that the C-type lectin domain of CLECSF8 was responsible for its intracellular retention. Although CLECSF8 does not contain a signaling motif in its cytoplasmic domain, we show that this receptor is capable of inducing signaling via Syk kinase in myeloid cells and that it can induce phagocytosis, proinflammatory cytokine production, and the respiratory burst. These data therefore indicate that CLECSF8 functions as an activation receptor on myeloid cells and associates with a novel adaptor molecule. Characterization of the CLECSF8-deficient mice and screening for ligands using oligosaccharide microarrays did not provide further insights into the physiological function of this receptor.

Original languageEnglish
Pages (from-to)25964-25974
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number31
DOIs
Publication statusPublished - 27 Jul 2012

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