The Autoimmune Regulator (AIRE), Which Is Defective in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients, Is Expressed in Human Epidermal and Follicular Keratinocytes and Associates With the Intermediate Filament Protein Cytokeratin 17
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2011
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Resumo |
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is caused by mutation of the autoimmune regulator (AIRE) gene, is a highly variable disease characterized by multiple endocrine failure, chronic mucocutaneous candidiasis, and various ectodermal defects. AIRE is a transcriptional regulator classically expressed in medullary thymic epithelial cells, monocytes, macrophages, and dendritic cells. Previous studies have suggested that AIRE can shuttle between the nucleus and cytoplasm of cells, although its cytoplasmic functions are poorly characterized. Through mass spectrometry analysis of proteins co-immunoprecipitating with cytoplasmic AIRE, we identified a novel association of AIRE with the intermediate filament protein cytokeratin 17 (K17) in the THP-1 monocyte cell line. We confirmed AIRE expression in HaCaT epidermal keratinocytes, as well as its interaction with K17. Confocal microscopy of human fetal and adult scalp hair follicles demonstrated a cytoplasmic pattern of AIRE staining that moderately colocalized with K17. The cytoplasmic association of AIRE with the intermediate filament network in human epidermal and follicular keratinocytes may provide a new path to understanding the ectodermal abnormalities associated with the APECED syndrome. (Am J Pathol 2011, 178:983-988; DOI: 10.1016/j.ajpath.2010.12.007) Children`s Hospital of Philadelphia Children`s Hospital of Philadelphia Jeffrey Modell Diagnostic Center Jeffrey Modell Diagnostic Center CAPES Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[09/51747-3] CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico[501332/2010-3] Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Penn Skin Disease Research Center[NIAMS P30 AR057217] Penn Skin Disease Research Center |
Identificador |
AMERICAN JOURNAL OF PATHOLOGY, v.178, n.3, p.983-988, 2011 0002-9440 http://producao.usp.br/handle/BDPI/28246 10.1016/j.ajpath.2010.12.007 |
Idioma(s) |
eng |
Publicador |
AMER SOC INVESTIGATIVE PATHOLOGY, INC |
Relação |
American Journal of Pathology |
Direitos |
restrictedAccess Copyright AMER SOC INVESTIGATIVE PATHOLOGY, INC |
Palavras-Chave | #PACHYONYCHIA-CONGENITA #IMMUNOLOGICAL SYNAPSE #KERATIN-17 #MUTATIONS #ACTIN #GENE #Pathology |
Tipo |
article original article publishedVersion |