| First Author | Kinoshita D | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 7 | Pages | 3995-4002 |
| PubMed ID | 16547234 | Mgi Jnum | J:129879 |
| Mgi Id | MGI:3770343 | Doi | 10.4049/jimmunol.176.7.3995 |
| Citation | Kinoshita D, et al. (2006) Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance. J Immunol 176(7):3995-4002 |
| abstractText | IkappaB kinase (IKK) alpha exhibits diverse biological activities through protein kinase-dependent and -independent functions, the former mediated predominantly through a noncanonical NF-kappaB activation pathway. The in vivo function of IKKalpha, however, still remains elusive. Because a natural strain of mice with mutant NF-kappaB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in the thymic stroma, we speculated that the NIK-IKKalpha axis might constitute an essential step in the thymic organogenesis that is required for the establishment of self-tolerance. An autoimmune disease phenotype was induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice. The thymic microenvironment that caused autoimmunity in an IKKalpha-dependent manner was associated with defective processing of NF-kappaB2, resulting in the impaired development of thymic epithelial cells. Thus, our results demonstrate a novel function for IKKalpha in thymic organogenesis for the establishment of central tolerance that depends on its protein kinase activity in cooperation with NIK. |
