Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation
Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation
复制标题
DOI：
10.1186/ar1472
复制
发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Glant, TT
中科院分区：
文献类型：
--
作者：
Adarichev, VA;Vermes, C;Glant, TT
在这里，我们使用高密度寡核苷酸阵列询问整个小鼠基因组，对小鼠自身免疫性关节炎的起始、急性和慢性阶段的差异基因表达进行了广泛的研究。用蛋白多糖免疫的BALB/c关节炎小鼠的淋巴细胞过继转移诱导严重联合免疫缺陷小鼠的关节炎。在这个独特的系统中，只有蛋白多糖特异的淋巴细胞从关节炎小鼠转移到缺乏获得性免疫但在相同(BALB/c)遗传背景下具有完整先天免疫的同基因免疫缺陷受者。因此，甚至在炎症发生之前，就可以准确地监测对移行到关节内的供者淋巴细胞的差异基因表达。过继传播性疾病的起始期(关节肿胀开始前几天)以37个基因的差异表达为特征，主要与趋化因子、干扰素-γ和肿瘤坏死因子-α信号以及T细胞功能有关。这些基因被指定为早期关节炎的标志性基因，因为它们可以区分幼稚状态和关节炎前期状态。急性关节炎症的特征是256个基因至少表达两倍，21个基因下调，而在慢性关节炎中，共有418个基因表达差异，上调和下调的基因比例相等。炎症相关基因和关节炎相关基因的层次聚类和功能分类表明，最常见的生物学活性表现为编码白细胞介素素、趋化因子受体和配体的基因，以及参与抗原识别和处理的基因。
We present here an extensive study of differential gene expression in the initiation, acute and chronic phases of murine autoimmune arthritis with the use of high-density oligonucleotide arrays interrogating the entire mouse genome. Arthritis was induced in severe combined immunodeficient mice by using adoptive transfer of lymphocytes from proteoglycan-immunized arthritic BALB/c mice. In this unique system only proteoglycan-specific lymphocytes are transferred from arthritic mice into syngeneic immunodeficient recipients that lack adaptive immunity but have intact innate immunity on an identical ( BALB/ c) genetic background.Differential gene expression in response to donor lymphocytes that migrated into the joint can therefore be monitored in a precisely timed manner, even before the onset of inflammation. The initiation phase of adoptively transferred disease ( several days before the onset of joint swelling) was characterized by differential expression of 37 genes, mostly related to chemokines, interferon-gamma and tumor necrosis factor-alpha signaling, and T cell functions. These were designated early arthritis 'signature' genes because they could distinguish between the naive and the pre-arthritic state. Acute joint inflammation was characterized by at least twofold overexpression of 256 genes and the downregulation of 21 genes, whereas in chronic arthritis a total of 418 genes with an equal proportion of upregulated and downregulated transcripts were expressed differentially.Hierarchical clustering and functional classification of inflammation- related and arthritis-related genes indicated that the most common biological activities were represented by genes encoding interleukins, chemokine receptors and ligands, and by those involved in antigen recognition and processing.