Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/52104
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Type: Journal article
Title: Reduced thymic aire expression and abnormal NF-κB2 signaling in a model of systemic autoimmunity
Other Titles: Reduced thymic aire expression and abnormal NF-kappaB2 signaling in a model of systemic autoimmunity
Author: Fletcher, A.
Seach, N.
Reiseger, J.
Lowen, T.
Hammett, M.
Scott, H.
Boyd, R.
Citation: Journal of Immunology, 2009; 182(5):2690-2699
Publisher: Amer Assoc Immunologists
Issue Date: 2009
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
Anne L. Fletcher, Natalie Seach, Jessica J. Reiseger, Tamara E. Lowen, Maree V. Hammett, Hamish S. Scott and Richard L. Boyd
Abstract: The 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.
Keywords: Lymphoid Tissue
Thymus Gland
Stromal Cells
Epithelial Cells
Animals
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Inbred NZB
Mice
Autoimmune Diseases
Disease Models, Animal
Disease Progression
Transcription Factors
Immunophenotyping
Signal Transduction
Transcription, Genetic
Down-Regulation
NF-kappa B p52 Subunit
Rights: Copyright © 2009 by The American Association of Immunologists, Inc.
DOI: 10.4049/jimmunol.0801752
Appears in Collections:Aurora harvest
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