Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family
Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family
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DOI：
10.1074/jbc.m115.643361
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发表时间：
2015-09-04
影响因子：
4.8
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Niizuma, Kouta;Tahara-Hanaoka, Satoko;Shibuya, Akira
募集循环单核细胞和中性粒细胞到感染部位是宿主防御感染的必要条件。在这里，我们发现了一个先前未注释的基因，该基因编码免疫球蛋白样受体，命名为CD300H，位于CD300基因簇中。CD300H具有短的细胞质尾部，与信号转导蛋白DAP12和DAP10相关。CD300H在CD16（+）单核细胞和骨髓树突状细胞上表达。用抗CD300H单克隆抗体将CD300H连接到CD16（+）单核细胞和骨髓树突状细胞上，诱导中性粒细胞趋化剂的产生。有趣的是，CD300H在健康受试者中的表达存在差异，健康受试者可根据“阳性”和“阴性”表达分为两组。基因组序列分析显示，在一个或两个等位基因的内含子1的剪接供体位点上存在单核苷酸替换（rs905709 (G -> a)）。国际HapMap项目数据库显示，单核苷酸多态性（SNP） rs905709等位基因的纯合子（“阴性”表达）在北京的汉人、东京的日本人和欧洲人中非常常见（A/A基因型频率分别为0.349、0.167和0.138），但在撒哈拉以南非洲人群中极为罕见。总之，这些结果表明CD300H可能在先天免疫中发挥重要作用，至少在携带CD300H的G/G或G/A基因型的人群中是如此。
Recruitment of circulating monocytes and neutrophils to infection sites is essential for host defense against infections. Here, we identified a previously unannotated gene that encodes an immunoglobulin-like receptor, designated CD300H, which is located in the CD300 gene cluster. CD300H has a short cytoplasmic tail and associates with the signaling adaptor proteins, DAP12 and DAP10. CD300H is expressed on CD16(+) monocytes and myeloid dendritic cells. Ligation of CD300H on CD16(+) monocytes and myeloid dendritic cells with anti-CD300H monoclonal antibody induced the production of neutrophil chemoattractants. Interestingly, CD300H expression varied among healthy subjects, who could be classified into two groups according to "positive" and "negative" expression. Genomic sequence analysis revealed a single-nucleotide substitution (rs905709 (G -> A)) at a splice donor site on intron 1 on either one or both alleles. The International HapMap Project database has demonstrated that homozygosity for the A allele of single nucleotide polymorphism (SNP) rs905709 ("negative" expression) is highly frequent in Han Chinese in Beijing, Japanese in Tokyo, and Europeans (A/A genotype frequencies 0.349, 0.167, and 0.138, respectively) but extremely rare in Sub-Saharan African populations. Together, these results suggest that CD300H may play an important role in innate immunity, at least in populations that carry the G/G or G/A genotype of CD300H.