Ronninger M, Eklöw C, Lorentzen J C, Klareskog L, Padyukov L
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Genes Immun. 2008 Jul;9(5):412-8. doi: 10.1038/gene.2008.32. Epub 2008 May 15.
Dendritic cell immunoreceptor (DCIR) deficiency is related to development of autoimmune disorders and DCIR gene polymorphisms are associated with rheumatoid arthritis (RA). We analyzed the mRNA expression from the four known transcripts of DCIR in IFN-gamma-treated human leukocytes together with fine mapping across the locus. RA patients and healthy controls were genotyped for several single nucleotide polymorphisms (SNPs) in DCIR and flanking regions. mRNA expression in peripheral blood mononuclear cells (PBMCs), stimulated with gamma-interferon (IFN-gamma) in vitro, was determined by transcript-specific PCR. Our data reveal that IFN-gamma significantly downregulates the average expression of transcripts DCIR_v1, DCIR_v2, DCIR_v3 and DCIR_v4 (P<0.0001 for v1, P<0.02 for v2, P<0.0001 for v3, P<0.001 for _v4, patients and controls, Wilcoxon signed-rank). The expression of DCIR showed significant association with variations in the gene. Cells with the RA-associated allele rs2024301 exhibit a significant increase in the expression of DCIR_v4. We also present a new fifth isoform lacking exons 2, 3 and 4. This data illustrate that common genetic variations may influence DCIR mRNA expression. We also show that the expression is regulated by the inflammatory mediator IFN-gamma, affecting all four transcripts and that this was independent of genotype.
树突状细胞免疫受体（DCIR）缺陷与自身免疫性疾病的发生发展相关，且DCIR基因多态性与类风湿关节炎（RA）有关。我们分析了经γ干扰素（IFN-γ）处理的人白细胞中DCIR四个已知转录本的mRNA表达情况，并对该基因座进行了精细定位。对RA患者和健康对照者的DCIR及其侧翼区域的多个单核苷酸多态性（SNP）进行了基因分型。通过转录本特异性PCR测定外周血单核细胞（PBMC）在体外经γ干扰素（IFN-γ）刺激后的mRNA表达。我们的数据显示，IFN-γ显著下调转录本DCIR_v1、DCIR_v2、DCIR_v3和DCIR_v4的平均表达（v1的P<0.0001，v2的P<0.02，v3的P<0.0001，v4的P<0.001，患者和对照，Wilcoxon符号秩检验）。DCIR的表达与该基因的变异存在显著关联。携带与RA相关等位基因rs2024301的细胞中DCIR_v4的表达显著增加。我们还发现了一种新的第五种异构体，它缺少外显子2、3和4。这些数据表明常见的基因变异可能会影响DCIR的mRNA表达。我们还表明，该表达受炎症介质IFN-γ的调节，影响所有四个转录本，且这与基因型无关。
