Negative regulation of leucocyte functions by CD33-related siglecs.
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-alpha 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.
Avril
T
T
Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.
Attrill
H
H
Zhang
J
J
Raper
A
A
Crocker
P R
PR
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037102:Lectins / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008565:Membrane Proteins; D011971:Receptors, Immunologic / Q000276:immunology; D063268:Sialic Acid Binding Ig-like Lectin 3; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D051193:Toll-Like Receptors / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D037102:Lectins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D063268:Sialic Acid Binding Ig-like Lectin 3; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C110546:TYROBP protein, human; D051193:Toll-Like Receptors