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T-cell receptor repertoire analysis of CD4-positive T cells from blood and an affected organ in an autoimmune mouse model
Genes to Cells ( IF 2.1 ) Pub Date : 2023-11-01 , DOI: 10.1111/gtc.13079
Tatsuya Ishikawa 1, 2 , Kenta Horie 1 , Yuki Takakura 1 , Houko Ohki 1, 2 , Yuya Maruyama 1, 2 , Mio Hayama 1, 2 , Maki Miyauchi 1, 2 , Takahisa Miyao 1, 2 , Naho Hagiwara 1 , Tetsuya J Kobayashi 3 , Nobuko Akiyama 1, 2 , Taishin Akiyama 1, 2
Affiliation  

One hallmark of some autoimmune diseases is the variability of symptoms among individuals. Organs affected by the disease differ between patients, posing a challenge in diagnosing the affected organs. Although numerous studies have investigated the correlation between T cell antigen receptor (TCR) repertoires and the development of infectious and immune diseases, the correlation between TCR repertoires and variations in disease symptoms among individuals remains unclear. This study aimed to investigate the correlation of TCRα and β repertoires in blood T cells with the extent of autoimmune signs that varies among individuals. We sequenced TCRα and β of CD4+CD44highCD62Llow T cells in the blood and stomachs of mice deficient in autoimmune regulator (Aire) (AIRE KO), a mouse model of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Data analysis revealed that the degree of similarity in TCR sequences between the blood and stomach varied among individual AIRE KO mice and reflected the extent of T cell infiltration in the stomach. We identified a set of TCR sequences whose frequencies in blood might correlate with extent of the stomach manifestations. Our results propose a potential of using TCR repertoires not only for diagnosing disease development but also for diagnosing affected organs in autoimmune diseases.

中文翻译:

自身免疫小鼠模型中血液和受影响器官中 CD4 阳性 T 细胞的 T 细胞受体库分析

一些自身免疫性疾病的特点之一是个体之间症状的变异性。患者受疾病影响的器官各不相同,这给诊断受影响的器官带来了挑战。尽管大量研究已经调查了 T 细胞抗原受体 (TCR) 库与传染病和免疫性疾病发展之间的相关性,但 TCR 库与个体疾病症状变异之间的相关性仍不清楚。本研究旨在探讨血液 T 细胞中 TCRα 和 β 库与个体间差异的自身免疫体征程度的相关性。我们对缺乏自身免疫调节因子 ( Aire )的小鼠 (AIRE KO) 的血液和胃中CD4 + CD44CD62LT 细胞的 TCRα 和 β 进行了测序,该小鼠是人类自身免疫性多内分泌病-念珠菌病-外胚层营养不良的小鼠模型。数据分析显示,AIRE KO 小鼠个体之间血液和胃部 TCR 序列的相似程度存在差异,反映了胃部 T 细胞浸润的程度。我们鉴定了一组 TCR 序列,其在血液中的频率可能与胃部表现的程度相关。我们的结果表明,使用 TCR 库不仅可以诊断疾病的发展,还可以诊断自身免疫性疾病中受影响的器官。
更新日期:2023-11-01
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