The siglecs (sialic acid-binding Ig-like lectins) are a family of transmembrane receptors expressed in the haemopoietic, immune and nervous systems. The CD33-related siglecs are a distinct subset mostly expressed in the innate immune system where they can function as inhibitory receptors by suppressing the signalling mediated by receptors coupled with ITAMs (immunoreceptor tyrosine-based activation motifs). CD33-related siglecs contain ITIMs (immunoreceptor tyrosine-based inhibitory motifs) that recruit and activate SHP-1 [SH2 (Src homology 2) domain-containing phosphatase-1] and SHP-2. In addition, the ITIMs of CD33-related siglecs can suppress siglec-dependent adhesion of sialylated ligands and mediate endocytosis. Siglec-H is a recently characterized murine CD33-related endocytic receptor that lacks intrinsic tyrosine-based signalling motifs and is expressed selectively on PDCs (plasmacytoid dendritic cells). Siglec-H depends on DAP12 (DNAX-activating protein of 12 kDa) for surface expression and cross-linking with anti-siglec-H antibodies can selectively inhibit interferon-α production by PDCs following TLR9 (Toll-like receptor 9) ligation. Thus CD33-related siglecs are able to mediate diverse inhibitory functions of leucocytes in the innate immune system via both ITIM-dependent and -independent pathways.
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December 2006
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Conference Article|
October 25 2006
Negative regulation of leucocyte functions by CD33-related siglecs
T. Avril;
T. Avril
1Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
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H. Attrill;
H. Attrill
2Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
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J. Zhang;
J. Zhang
3Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
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A. Raper;
A. Raper
4Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
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P.R. Crocker
P.R. Crocker
1
5Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
1To whom correspondence should be addressed (email p.r.crocker@dundee.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 31 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1024–1027.
Article history
Received:
July 31 2006
Citation
T. Avril, H. Attrill, J. Zhang, A. Raper, P.R. Crocker; Negative regulation of leucocyte functions by CD33-related siglecs. Biochem Soc Trans 1 December 2006; 34 (6): 1024–1027. doi: https://doi.org/10.1042/BST0341024
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