| First Author | Kajiura F | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 4 | Pages | 2067-75 |
| PubMed ID | 14764671 | Mgi Jnum | J:87993 |
| Mgi Id | MGI:3028796 | Doi | 10.4049/jimmunol.172.4.2067 |
| Citation | Kajiura F, et al. (2004) NF-kappaB-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner. J Immunol 172(4):2067-75 |
| abstractText | Physical contact between thymocytes and the thymic stroma is essential for T cell maturation and shapes the T cell repertoire in the periphery. Stromal elements that control these processes still remain elusive. We used a mouse strain with mutant NF-kappaB-inducing kinase (NIK) to examine the mechanisms underlying the breakdown of self-tolerance. This NIK-mutant strain manifests autoimmunity and disorganized thymic structure with abnormal expression of Rel proteins in the stroma. Production of immunoregulatory T cells that control autoreactive T cells was impaired in NIK-mutant mice. The autoimmune disease seen in NIK-mutant mice was reproduced in athymic nude mice by grafting embryonic thymus from NIK-mutant mice, and this was rescued by supply of exogenous immunoregulatory T cells. Impaired production of immunoregulatory T cells by thymic stroma without normal NIK was associated with altered expression of peripheral tissue-restricted Ags, suggesting an essential role of NIK in the thymic microenvironment in the establishment of central tolerance. |
