Mingzhao Zhu, Robert K. Chin, Peter A. Christiansen, James C. Lo, Xiaojuan Liu, Carl Ware, Ulrich Siebenlist, Yang-Xin Fu
J Clin Invest.
2006;
116(11):2964–2971
doi:10.1172/JCI28326
This article Copyright © 2006, The American Society for Clinical Investigation
Abstract
|
Full text
|
PDF
|
Supplemental material
N
F-κB2–deficient mice have impaired T and B cell responses. We found, however, that in these mice there was severe infiltration of lymphocytes into multiple organs and increased activity of autoantibodies to peripheral tissue antigens in a manner similar to that of autoimmune regulator–deficient (Aire-deficient) mice. We further demonstrated that NF-κB2 was required for thymic Aire gene transcriptional regulation. The Nfkb2–/– thymus had distinct cortical and medullar structures, but reduced Aire and target gene expression of peripheral tissue antigens. Engraftment of Nfkb2–/– thymic stroma to nude mice recapitulated the autoimmune phenotype of the native Nfkb2–/– mice, confirming a key defect in central tolerance. Lymphotoxin β receptor (LTβR) ligation–induced Aire gene expression was also largely abolished in the absence of NF-κB2. Thus NF-κB2 downstream of LTβR plays an important role in the regulation of central tolerance in an Aire-dependent manner.
This file is in Adobe Acrobat (PDF) format.
If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not
allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users:
Right-click on the Download link and choose the option that says something like "Save Link As...".
Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you
configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can
usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
