共查询到20条相似文献,搜索用时 31 毫秒
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AIRE's CARD revealed, a new structure for central tolerance provokes transcriptional plasticity 总被引:3,自引:0,他引:3
Ferguson BJ Alexander C Rossi SW Liiv I Rebane A Worth CL Wong J Laan M Peterson P Jenkinson EJ Anderson G Scott HS Cooke A Rich T 《The Journal of biological chemistry》2008,283(3):1723-1731
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A specific anti-Aire antibody reveals aire expression is restricted to medullary thymic epithelial cells and not expressed in periphery 总被引:3,自引:0,他引:3
Hubert FX Kinkel SA Webster KE Cannon P Crewther PE Proeitto AI Wu L Heath WR Scott HS 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(6):3824-3832
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. 相似文献
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The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression 总被引:2,自引:0,他引:2
Org T Chignola F Hetényi C Gaetani M Rebane A Liiv I Maran U Mollica L Bottomley MJ Musco G Peterson P 《EMBO reports》2008,9(4):370-376
Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus. 相似文献
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Nagafuchi S Katsuta H Koyanagi-Katsuta R Yamasaki S Inoue Y Shimoda K Ikeda Y Shindo M Yoshida E Matsuo T Ohno Y Kogawa K Anzai K Kurisaki H Kudoh J Harada M Shimizu N 《Microbiology and immunology》2006,50(12):979-987
The autoimmune regulator (AIRE) gene is a gene responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Here we show that AIRE is expressed in human peripheral CD4-positive T-cells, and most highly in antigen-and interleukin 2-stimulated T (IL-2T) cells. Mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated in IL-2T cells and the expression of the AIRE gene was inhibited by a specific p38 MAPK inhibitor (SB203580), thereby indicating that AIRE gene expression is controlled by the MAPK pathway in IL-2T cells. These data suggested the possible significance of the AIRE gene in the peripheral immune system. 相似文献
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A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients 总被引:9,自引:0,他引:9
M. C. Rosatelli Alessandra Meloni Antonella Meloni Marcella Devoto Antonio Cao H. S. Scott Pärt Peterson Maarit Heino Kai J. E. Krohn Kentaro Nagamine J. Kudoh Nobuyoshi Shimizu Stylianos E. Antonarakis 《Human genetics》1998,103(4):428-434
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Yamaguchi Y Takayanagi A Chen J Sakai K Kudoh J Shimizu N 《Experimental cell research》2011,(14):2019-2030
In the human thymus, AIRE (autoimmune regulator) gene is expressed in a very limited type of medullary thymic epithelial cells (mTECs) and no cognate cell lines are available, hence the molecular analysis of AIRE gene function has been difficult. To improve this situation, we attempted to isolate Aire-expressing cells and established three cell lines (Aire+TEC1, Aire+TEC2, Aire+DC) from the abnormally enlarged thymus, which was developed in the transgenic mice expressing SV40 T-antigen driven by the mouse Aire gene promoter. When these Aire+ cell lines were co-cultured with fresh thymocytes, they adhered to the majority of thymocytes and induced apoptosis as if negative selection of T-cells in the thymus is occurring in vitro. Further analysis revealed that these Aire+ cell lines are derived from mTECs and exhibit characteristic natures of “antigen presenting cells” including several distinct abilities: to express a variety of peripheral tissue-specific antigens, to produce immunoproteasome and immunological synapse, and to express some of TNFSFs (tumor necrosis factor super families). Thus, the newly established Aire+ cell lines will be invaluable for the further detailed analysis of AIRE gene function in the central tolerance of immunity and autoimmune disease. 相似文献
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Francesca Bianchi Michele Sommariva Loris De Cecco Tiziana Triulzi Sandra Romero-Cordoba Elda Tagliabue 《Cell cycle (Georgetown, Tex.)》2016,15(23):3220-3229
The autoimmune regulator gene (AIRE) plays a fundamental role in tolerance by promoting the expression of tissue-specific antigens in medullary thymic epithelial cells (mTECs). Recently, AIRE expression was detected also in human keratinocytes and in tumors originating in stratified epithelia. Here, we tested whether AIRE is expressed in cancer cells. We analyzed AIRE expression in cancer cases from The Cancer Genome Atlas (TCGA) RNA-seq dataset and we found association with better outcome. AIRE protein expression was verified by immunohistochemistry in a cohort of 39 human breast cancer specimens and its prognostic relevance was confirmed in microarray-based gene expression data set NKI-295 and KM-Plotter. Both in the RNA-seq and gene expression datasets analyzed, AIRE expression was an independent strong prognostic factor for relapse-free survival (RFS), particularly in estrogen receptor-positive tumors. Enrichment of translation-related pathways was observed in AIRE-expressing tumors by Ingenuity Pathway Analysis and a significant increase of cells in G1 phase and activation of caspase cascades was induced by AIRE transfection in breast cancer luminal cell lines, suggesting that AIRE-induced over-translation of proteins lead to cycle arrest and apoptosis. These data are the first to identify AIRE expression in breast cancer and an association with prognosis. 相似文献
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Brahmaraju M Bhagya KP Titus S Sebastian A Devi AN Laloraya M Kumar PG 《Biochimie et biologie cellulaire》2011,89(4):411-422
The autoimmune regulator gene Aire shows predominant expression in thymus and other immunologically relevant tissues, and is assigned the major function of programming autoreactive T-cell deletion. However, the expression of this gene in tissues outside the immune system raises a question about its possible function beyond the T-cell deletion dogma. We detected Aire in mouse testis, and the expression of AIRE protein was remarkably high in postmeiotic germ cells. Sequencing results indicate that testis expressed Aire variant 1a. AIRE could be detected in spermatozoa, with heavy localization on the principal acrosomal domains. Mouse oocytes stained negatively for AIRE before fertilization, but stained positively for AIRE 30?min after fertilization. In the zygote, the levels of AIRE correlated negatively with cyclin B2 levels. Goat testicular lysates spiked with recombinant human AIRE exhibited augmented cyclin B2 degradation in the presence of protease inhibitors, which was inhibited by MG-132, indicating the operation of proteasomal pathways. Thus, this study identifies a correlation between the presence of AIRE and proteasomal breakdown of cyclin B2, which leads us to speculate that cyclin B2 could be a target of AIRE's E3-ubiquitin ligase activity. 相似文献