| First Author | Zhu M | Year | 2006 |
| Journal | J Clin Invest | Volume | 116 |
| Issue | 11 | Pages | 2964-71 |
| PubMed ID | 17039258 | Mgi Jnum | J:115011 |
| Mgi Id | MGI:3690531 | Doi | 10.1172/JCI28326 |
| Citation | Zhu M, et al. (2006) NF-kappaB2 is required for the establishment of central tolerance through an Aire-dependent pathway. J Clin Invest 116(11):2964-71 |
| abstractText | NF-kappaB2-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-kappaB2 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 beta receptor (LTbetaR) ligation-induced Aire gene expression was also largely abolished in the absence of NF-kappaB2. Thus NF-kappaB2 downstream of LTbetaR plays an important role in the regulation of central tolerance in an Aire-dependent manner. |
