Expression of AIRE gene in peripheral monocyte/dendritic cell lineage

Kogawa, Kazuhiko; Nagafuchi, Seiho; Katsuta, Hitoshi; Kudoh, Jun; Tamiya, Sadafumi; Sakai, Yumiko; Shimizu, Nobuyoshi; Harada, Mine

doi:10.1016/s0165-2478(01)00314-5

Cited by 115 publications

(87 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In accordance, human blood monocytes that express AIRE [58] were also increased in APS I patients as compared to control subjects. These results suggest that Aire either controls the expression of chemotaxis molecules or modulates the expression of DC-specific homing molecules.…”

Section: Discussionsupporting

confidence: 72%

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

et al. 2006

View full text Add to dashboard Cite

Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from endocrine and non-endocrine disorders due to mutations in the autoimmune regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary epithelial cells and in peripheral antigen-presenting cells, suggesting a role in both central and peripheral tolerance. We here report that Aire -/-dendritic cells (DC) activate naive T cells more efficiently than do Aire +/+ DC. Expression array analyses of Aire -/-DC revealed differential regulation of 68 transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1) transcript was up-regulated in Aire -/-DC. Concurrently, the expression of the VCAM-1 protein was up-regulated on both Aire -/-DC and monocytes from APS I patients. Blocking the interaction of VCAM-1 prevented enhanced Aire -/-DC stimulation of T cell hybridomas. We determined an increased number of DC in spleen and lymph nodes and of monocytes in the blood from Aire -/-mice, and an increased number of blood monocytes in APS I patients. Our findings imply a role for Aire in peripheral DC regulation of T cell activation, and suggest that Aire participates in peripheral tolerance.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35240_s.pdf IntroductionInactivation of the autoimmune regulator gene (AIRE) [1][2][3] causes autoimmunity in patients with autoimmune polyendocrine syndrome type I (APS I, APECED, OMIM 240300) and in a gene targeted mouse model [4,5]. APS I is a rare monogenic autosomal recessive disease without HLA association [6,7], which is prevalent in isolated populations [8][9][10]. APS I patients develop a progressive loss of tolerance against self antigens and suffer from multiorgan failures due to the immunological destruction of adrenals, parathyroid glands and b cells of the islets of Langerhans [11]. Many of the APS I organ-specific autoantigens have been identified and characterized [12,13]. In addition, as a sign of immune dysfunction, these patients have difficulties clearing Candida albicans infections in mucosal membranes [14]. Functional studies of AIRE suggest a role as a transcription factor and in vitro transactivating studies support this notion [15][16][17][18]. Moreover, the PHD1 domain of AIRE has been suggested to have an E3 ubiquitin ligase activity in cell-free assays [19], findings in variance with a recent report [20]. Aire is highly expressed in a subset of the medullary thymic epithelial cells (mTEC) as well as in DC in the spleen and lymph nodes [21][22][23][24], indicating a potential role in immunological tolerance.To characterize the function of Aire, we previously engineered an Aire-deficient mouse targeting the most common APS I mutation [4]. Aire-deficient mice develop multiple organ-specific autoantibodies and lymphocytic infiltrates, thus mimicking some of the features of human APS I [4]. Subsequently, the role of Aire in negative selection was demonstrated [5]. These findings were further supported using TCR transgenic mic...

show abstract

Section: Discussionsupporting

confidence: 72%

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Although in our previous study we reported that AIRE gene was expressed in peripheral monocyte-dendritic cells, expression of AIRE gene in peripheral Tcells was scarcely detected (13). However, by improving the CD4-positive T-cell isolation system and using a selected lot of fetal bovine serum, we are now stably and reproducibly able to detect the expression of the AIRE gene in peripheral CD4 ϩ T-cells.…”

mentioning

confidence: 86%

“…The samples were incubated overnight at 4 C with the anti-AIRE antibody diluted 1:200 in phosphate buffered saline (PBS). Subsequently, the samples were incubated with FITC-labeled swine anti-rabbit IgG (DAKO, Japan) or control serum and observed under differential interference contrast (DIC) or laser contrast microscope (13).…”

Section: Analysis Of Aire Gene Expression By Reverse Transcriptase Pomentioning

confidence: 99%

“…Since almost all patients with APECED associated with AIRE gene mutations are susceptible to candida infection (5,21) and the AIRE gene is expressed in peripheral lymph nodes, possibly dendritic cells and cells of monocyte-dendritic cell lineage, it is suggested that the AIRE gene may play an important role in the peripheral immune reactions dependent on dendritic cells (10,13). Surprisingly, as shown in this study, a high-level expression of the AIRE gene was induced in candida antigen and IL-2-stimulated T-cells (Fig.…”

Section: Expression Of Aire Gene In Established Cell Lines and Il-2t mentioning

confidence: 99%

See 1 more Smart Citation

Autoimmune Regulator (AIRE) Gene Is Expressed in Human Activated CD4⁺ T‐Cells and Regulated by Mitogen‐Activated Protein Kinase Pathway

Nagafuchi

Katsuta

Koyanagi-Katsuta

et al. 2006

Microbiology and Immunology

View full text Add to dashboard Cite

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.

show abstract

“…L'expression de AIRE est exclusivement retrouvée dans certains types cellulaires comme les CETm [3], les cellules B thymiques [11], les monocytes [12] et les cellules hépatiques foetales [13]. Plusieurs études ont permis d'appréhender les mécanismes de contrôle basal de l'expression de AIRE dans les CETm.…”

Section: Rôle Des Hormones Sexuelles Dans La Régulation De Aireunclassified

Prédisposition aux pathologies auto-immmunes

2017

View full text Add to dashboard Cite

> Les maladies auto-immunes sont un groupe d'environ 80 pathologies différentes affectant 5 à 8 % de la population. Elles sont dues à un dysfonctionnement du système immunitaire au niveau de la tolérance thymique. Le thymus est le site d'éducation des lymphocytes T. Cet apprentissage repose sur des interactions entre les lymphocytes T et les cellules épithéliales thymiques (CET) qui expriment les protéines spécifiques de tissus périphériques. Ce mécanisme complexe est appelé tolérance centrale. Les maladies autoimmunes présentent, pour la majorité d'entre elles, une forte prévalence féminine. La comparaison des transcriptomes thymiques de femmes et d'hommes met en évidence des différences d'expression des protéines spécifiques de tissus périphériques. Dans le thymus, l'expression de ces protéines est contrôlée par le modulateur de transcription AIRE (autoimmune regulator). Une analyse translationnelle de la relation entre le sexe, les hormones et AIRE, dans des modèles cellulaires humains et murins, montre qu'après la puberté, ce facteur est moins exprimé chez la femme que chez l'homme. Les estrogènes induisent une augmentation du nombre de sites de méthylation au niveau du promoteur de Aire réprimant ainsi son expression. À partir de la puberté, les femmes auraient une efficacité diminuée du processus de tolérance centrale, ce qui entraînerait un accroissement des cellules autoréactives et de leur susceptibilité aux maladies auto-immunes. Ces observations nous amènent à nous interroger sur les effets d'une exposition croissante aux perturbateurs endocriniens, molécules estrogen-like qui, en diminuant l'expression de AIRE, conduiraient à une augmentation de la fréquence des maladies auto-immunes. < Maladies auto-immunes : une forte prévalence féminineLes maladies auto-immunes touchent 5 à 8 % de la population en Europe Occidentale et aux États-Unis. Elles comprennent 70 à 80 pathologies différentes, comme la polyarthrite rhumatoïde, le lupus érythémateux disséminé, la sclérose en plaque, le diabète de type 1, le psoriasis, la maladie de Crohn et la myasthé-nie grave. Bien qu'elles présentent une grande disparité en ce qui concerne les organes ou systèmes ciblés, les auto-anticorps sériques produits et la réponse aux traitements, une caractéris-tique épidémiologique commune a été mise en évidence pour un grand nombre de ces pathologies : une forte prévalence féminine [1] (Tableau I). Cette prédominance féminine connue depuis des décennies demeure inexpliquée bien que de nombreuses hypothèses aient été émises impliquant l'environnement hormonal, le microchimérisme foetal, l'inactivation et/ou des anomalies du chromosome X. Le système immunitaire a pour fonction de protéger l'organisme contre des infections à travers des réponses innées et/ou adaptatives. Toutefois, il est clairement établi que les maladies autoimmunes se développent suite à une rupture dans les mécanismes de tolérance centrale ou périphérique du système immunitaire. Dans chacune de ces pathologies, une inflammation chronique ou périodique contribu...

show abstract

Expression of AIRE gene in peripheral monocyte/dendritic cell lineage

Cited by 115 publications

References 8 publications

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Autoimmune Regulator (AIRE) Gene Is Expressed in Human Activated CD4⁺ T‐Cells and Regulated by Mitogen‐Activated Protein Kinase Pathway

Prédisposition aux pathologies auto-immmunes

Contact Info

Product

Resources

About

Expression of AIRE gene in peripheral monocyte/dendritic cell lineage

Cited by 115 publications

References 8 publications

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Autoimmune Regulator (AIRE) Gene Is Expressed in Human Activated CD4+ T‐Cells and Regulated by Mitogen‐Activated Protein Kinase Pathway

Prédisposition aux pathologies auto-immmunes

Contact Info

Product

Resources

About

Autoimmune Regulator (AIRE) Gene Is Expressed in Human Activated CD4⁺ T‐Cells and Regulated by Mitogen‐Activated Protein Kinase Pathway