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. Horsnell, 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

64 Citations (Scopus)

Abstract

CLECSF8 is a poorly characterised 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 (DC). 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 signalling 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 signalling adaptor molecule, including DAP10, DAP12, or the FcR¿ chain, and we found that the C-type lectin domain of CLECSF8 was responsible for its intracellular retention. Although CLECSF8 does not contain a signalling motif in its cytoplasmic domain, we show that this receptor is capable of inducing signalling via Syk kinase in myeloid cells and that it can induce phagocytosis, pro-inflammatory 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. Characterisation 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
JournalThe Journal of Biological Chemistry
Volume287
Issue number31
Early online date11 Jun 2012
DOIs
Publication statusPublished - 27 Jul 2012

    Fingerprint

Keywords

  • cytokine
  • inflammation
  • innate immunity
  • phagocytosis
  • respiratory burst
  • signalling
  • C-type lectin
  • syk kinase
  • cellular activation
  • mouse phenotype

Cite this

Graham, L. M., Gupta, V., Schafer, G., Reid, D. M., Kimberg, M., Dennehy, K. M., Horsnell, W. G., Guler, R., Campanero-Rhodes, M. A., Palma, A. S., Feizi, T., Kim, S. K., Sobieszczuk, P., Willment, J. A., & Brown, G. D. (2012). The C-type lectin receptor CLECSF8(CLEC4D) is expressed by myeloid cells and triggers cellular activation through SYK kinase. The Journal of Biological Chemistry, 287(31), 25964-25974. https://doi.org/10.1074/jbc.M112.384164