Negative regulation of leucocyte functions by CD33-related siglecs
Negative regulation of leucocyte functions by CD33-related siglecs
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DOI：
10.1042/bst0341024
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发表时间：
2006-12-01
影响因子：
3.9
通讯作者：
Crocker, P. R.
中科院分区：
文献类型：
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作者：
Avril, T.;Attrill, H.;Crocker, P. R.
siglecs（唾液酸结合Ig样凝集素）是在造血、免疫和神经系统中表达的跨膜受体家族。CD 33相关的单克隆细胞是主要在先天免疫系统中表达的独特亚群，在先天免疫系统中它们可以通过抑制由与ITAM（基于免疫受体酪氨酸的活化基序）偶联的受体介导的信号传导而作为抑制性受体起作用。CD 33相关的单克隆细胞含有ITIM（基于免疫受体酪氨酸的抑制基序），其募集并激活SHP-1 [含SH 2（Src同源2）结构域的磷酸酶-1]和SHP-2。此外，CD 33相关的siglecs的ITIM可以抑制唾液酸化配体的siglec-dependent粘附并介导内吞作用。Siglec-H是最近表征的鼠CD 33相关内吞受体，其缺乏内在的基于酪氨酸的信号传导基序，并且选择性地在PDC（浆细胞样树突状细胞）上表达。Siglec-H依赖于DAP 12（12 kDa的DNA活化蛋白）进行表面表达，并且与抗siglec-H抗体的交联可以选择性地抑制TLR 9（Toll样受体9）连接后PDC产生的干扰素-α。因此，CD 33相关的单细胞能够通过ITIM依赖性和非依赖性途径介导先天免疫系统中白细胞的多种抑制功能。
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-depenclent 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.