title: 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.
abstract: 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.
authors.affiliation: Division of Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Vipul
authors.initials: V
authors.lastname: Kumar
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pedroza
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mace
authors.forename: Steven
authors.initials: S
authors.lastname: Seeholzer
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
authors.forename: Aimee S
authors.initials: AS
authors.lastname: Payne
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
mesh_terms: D000328:Adult; D002460:Cell Line; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053537:Keratin-17 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D016884:Polyendocrinopathies, Autoimmune / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D053537:Keratin-17; D014157:Transcription Factors; D000096927:AIRE Protein