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dc.contributor.authorFletcher, A.-
dc.contributor.authorSeach, N.-
dc.contributor.authorReiseger, J.-
dc.contributor.authorLowen, T.-
dc.contributor.authorHammett, M.-
dc.contributor.authorScott, H.-
dc.contributor.authorBoyd, R.-
dc.identifier.citationJournal of Immunology, 2009; 182(5):2690-2699-
dc.description.abstractThe thymic stromal niche normally directs the production and export of a self-tolerant T cell repertoire. Many models of spontaneous autoimmunity, however, develop thymic architectural abnormalities before disease onset. Although this is suspected to affect central tolerance induction, creating an autoimmune predisposition, in-depth analysis of the microenvironment within these thymi is lacking, such that the mechanisms and likely direct effects on the T cell repertoire are unknown or speculative. Here we show that NZB mice, the first described model for systemic autoimmunity, demonstrate a complex thymic phenotype, including a lack of the autoimmune regulator (Aire), early defects in thymic epithelial cell (TEC) expansion, and evidence for altered NF-κB2 signaling. Analysis of medullary TEC revealed a numerical loss of the Aire-expressing MHC class IIhigh (mTEC-high) subset as well reduced Aire protein and mRNA per cell. RelB expression was also reduced, while chemokines CCL19 and CCL21 were increased. Unexpectedly, the proportion of cortex and medulla in the NZB mice was normal from 36 wk, despite worsening architectural abnormalities. These data show that the NZB defect is more complex than previously appreciated, segregating into early numerical TEC deficiencies that correct with age, late degeneration of the niche architecture that does not affect TEC number, and a persistent reduction in Aire and RelB expression per cell acquired upon mTEC-high differentiation.-
dc.description.statementofresponsibilityAnne L. Fletcher, Natalie Seach, Jessica J. Reiseger, Tamara E. Lowen, Maree V. Hammett, Hamish S. Scott and Richard L. Boyd-
dc.publisherAmer Assoc Immunologists-
dc.rightsCopyright © 2009 by The American Association of Immunologists, Inc.-
dc.subjectLymphoid Tissue-
dc.subjectThymus Gland-
dc.subjectStromal Cells-
dc.subjectEpithelial Cells-
dc.subjectMice, Inbred BALB C-
dc.subjectMice, Inbred C57BL-
dc.subjectMice, Inbred NOD-
dc.subjectMice, Inbred NZB-
dc.subjectAutoimmune Diseases-
dc.subjectDisease Models, Animal-
dc.subjectDisease Progression-
dc.subjectTranscription Factors-
dc.subjectSignal Transduction-
dc.subjectTranscription, Genetic-
dc.subjectNF-kappa B p52 Subunit-
dc.titleReduced thymic aire expression and abnormal NF-κB2 signaling in a model of systemic autoimmunity-
dc.title.alternativeReduced thymic aire expression and abnormal NF-kappaB2 signaling in a model of systemic autoimmunity-
dc.typeJournal article-
dc.identifier.orcidScott, H. [0000-0002-5813-631X]-
Appears in Collections:Aurora harvest
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