A Specific Anti-Aire Antibody Reveals Aire Expression Is Restricted to Medullary Thymic Epithelial Cells and Not Expressed in Periphery1

A Specific Anti-Aire Antibody Reveals Aire Expression Is Restricted to Medullary Thymic Epithelial Cells and Not Expressed in Periphery1
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一种特异性抗 Aire 抗体表明 Aire 表达仅限于胸腺髓质上皮细胞,在外周细胞中不表达1

DOI:
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发表时间:
2008
影响因子:
4.4
通讯作者:
H. Scott
H. Scott
中科院分区:
医学2区
文献类型:
--
作者:
F. Hubert;S. Kinkel;K. Webster;P. Cannon;P. Crewther;Anna I. Proeitto;Li Wu;W. Heath;H. Scott

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自身免疫性多内分泌病-念珠菌病-外胚层营养不良是由自身免疫调节基因AIRE突变引起的自身免疫性疾病。我们使用一种新的鼠Aire特异性鼠单克隆抗体检测了C57 BL/6小鼠不同器官(胸腺、脾脏和淋巴结)中Aire的表达。使用流式细胞术,直接荧光染料标记的mAb显示Aire在一个罕见的胸腺细胞亚群中表达,该亚群是CD 45 −,表达低水平的Ly 51,并且对于MHC-II和EpCam是高的。该亚群还表达一种特定的共刺激分子模式,包括CD 40、CD 80和PD-L1。免疫组化分析显示,Aire+细胞特异性定位于胸腺,或更准确地说,皮质-髓质交界处和髓质,与阴性选择的网站。虽然与以前的研究,低水平的Aire mRNA检测到所有的树突状细胞亚型,但lacZ染色,免疫组化和流式细胞术未能检测到Aire蛋白。在细胞水平上,Aire在细胞核内的核周斑点中表达。这份报告提供了Aire蛋白表达的第一个详细分析,突出了在组织和细胞水平上的精确位置。
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an autoimmune disorder caused by mutations in the autoimmune regulator gene AIRE. We examined the expression of Aire in different organs (thymus, spleen, and lymph nodes) in C57BL/6 mice, using a novel rat mAb, specific for murine Aire. Using flow cytometry, directly fluorochrome-labeled mAb revealed Aire expression in a rare thymic cellular subset that was CD45−, expressed low levels of Ly51, and was high for MHC-II and EpCam. This subset also expressed a specific pattern of costimulatory molecules, including CD40, CD80, and PD-L1. Immunohistochemical analysis revealed that Aire+ cells were specifically localized to the thymus or, more precisely, to the cortico-medulla junction and medulla, correlating with the site of negative selection. Although in agreement with previous studies, low levels of Aire mRNA was detected in all dendritic cell subtypes however lacZ staining, immunohistochemistry and flow cytometry failed to detect Aire protein. At a cellular level, Aire was expressed in perinuclear speckles within the nucleus. This report provides the first detailed analysis of Aire protein expression, highlighting the precise location at both the tissue and cellular level.
DOI: 10.1016/j.immuni.2005.07.005
发表时间: 2005-08-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者: Mathis, D