NF-kappa B2 is required for the establishment of central tolerance through an Aire-dependent pathway

作者：Zhu Mingzhao; Chin Robert K; Christiansen Peter A; Lo James C; Liu Xiaojuan; Ware Carl; Siebenlist Ulrich; Fu Yang Xin^*

来源：Journal of Clinical Investigation, 2006, 116(11): 2964-2971.

DOI：10.1172/JCI28326

NF-kappa B2-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-kappa B2 was required for thymic Aire gene transcriptional regulation. The Njkb2(-/-) thymus had distinct cortical and medullar structures, but reduced Aire and target gene expression of peripheral tissue antigens. Engraftment of Nfkb(-/-) thymic stroma to nude mice recapitulated the autoimmune phenotype of the native Nfkb2(-/-) mice, confirming a key defect in central tolerance. Lymphotoxin beta receptor (LT beta R) ligation-induced Aire gene expression was also largely abolished in the absence of NF-kappa B2. Thus NF-kappa B2 downstream of LTOR plays an important role in the regulation of central tolerance in an Aire-dependent manner.

• 出版日期2006-11
• 单位NIH