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,
* Division of Molecular and Medicine and
Division of Immunology, Walter and Eliza Hall Institute of Medical Research, and
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by fellowships from la Fondation pour la Recherche Medicale (to F.-X.H.), Australian Postgraduate Awards (to K.E.W. and S.A.K.), Howard Hughes Medical Institute international scholar (to W.R.H.), National Health and Medical Research Council fellowships (171601 and 461204), National Health and Medical Research Council program grants (257501 and 264573), Eurothymaide, 6th Framework Programme of the European Union, and the Nossal Leadership Award from the Walter and Eliza Hall Institute of Medical Research (to H.S.S.).
2 Address correspondence and reprint requests to Dr. François-Xavier Hubert and Dr. Hamish Scott, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. E-mail addresses: hubert{at}wehi.edu.au and hamish.scott{at}imvs.sa.gov.au
3 Current address: Immunology and Inflammation, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
4 Current address: Division of Molecular Pathology, Institute of Medical and Veterinary Science and The Hanson Institute, Box 14 Rundle Mall Post Office, Adelaide, South Australia 5000 and School of Medicine, University of Adelaide, South Australia 5005, Australia.
5 Abbreviations used in this paper: APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; APS I, autoimmune polyglandular syndrome type I; AIRE, autoimmune regulator; TEC, thymic epithelial cell; ES, embryonic stem; PGK-Neo, phosphoglycerate kinase neomycin; SIRP, signal regulatory protein; cTEC, cortical thymic epithelium; mTEC, medullar thymic epithelial cell; DC, dendritic cell.
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