Niizuma Kouta, Tahara-Hanaoka Satoko, Noguchi Emiko, Shibuya Akira
From the Departments of Immunology and the Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
From the Departments of Immunology and the Center for Tsukuba Advanced Research Alliance (TARA), the Japan Science and Technology Agency, CREST, and
J Biol Chem. 2015 Sep 4;290(36):22298-308. doi: 10.1074/jbc.M115.643361. Epub 2015 Jul 28.
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.
循环单核细胞和中性粒细胞募集到感染部位对于宿主抵御感染至关重要。在此,我们鉴定出一个先前未注释的基因,该基因编码一种免疫球蛋白样受体,命名为CD300H,它位于CD300基因簇中。CD300H具有短的细胞质尾巴,并与信号衔接蛋白DAP12和DAP10相关联。CD300H在CD16(+)单核细胞和髓样树突状细胞上表达。用抗CD300H单克隆抗体连接CD16(+)单核细胞和髓样树突状细胞上的CD300H可诱导中性粒细胞趋化因子的产生。有趣的是,健康受试者中CD300H的表达存在差异,根据“阳性”和“阴性”表达可分为两组。基因组序列分析显示,一个或两个等位基因的内含子1剪接供体位点存在单核苷酸替换(rs905709 (G → A))。国际人类基因组单体型图计划数据库表明,单核苷酸多态性(SNP)rs905709的A等位基因纯合子(“阴性”表达)在北京汉族、东京日本人及欧洲人中非常常见(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可能在固有免疫中发挥重要作用,至少在携带CD300H的G/G或G/A基因型的人群中如此。