Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
van der Post, Sjoerd
MetadataShow full item record
CitationJ. Immunol. 2014, 193 (5):2187-95
AbstractDown syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall's corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes.
DescriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the page
RightsArchived with thanks to Journal of immunology (Baltimore, Md. : 1950)
- Decreased AIRE expression and global thymic hypofunction in Down syndrome.
- Authors: Lima FA, Moreira-Filho CA, Ramos PL, Brentani H, Lima Lde A, Arrais M, Bento-de-Souza LC, Bento-de-Souza L, Duarte MI, Coutinho A, Carneiro-Sampaio M
- Issue date: 2011 Sep 15
- Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.
- Authors: Giménez-Barcons M, Casteràs A, Armengol Mdel P, Porta E, Correa PA, Marín A, Pujol-Borrell R, Colobran R
- Issue date: 2014 Oct 15
- Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance.
- Authors: Yano M, Kuroda N, Han H, Meguro-Horike M, Nishikawa Y, Kiyonari H, Maemura K, Yanagawa Y, Obata K, Takahashi S, Ikawa T, Satoh R, Kawamoto H, Mouri Y, Matsumoto M
- Issue date: 2008 Nov 24
- Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus.
- Authors: Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ
- Issue date: 2005 Aug 25
- An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus.
- Authors: Giraud M, Taubert R, Vandiedonck C, Ke X, Lévi-Strauss M, Pagani F, Baralle FE, Eymard B, Tranchant C, Gajdos P, Vincent A, Willcox N, Beeson D, Kyewski B, Garchon HJ
- Issue date: 2007 Aug 23