| First Author | Shen H | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 38 | Pages | 19090-19097 |
| PubMed ID | 31481626 | Mgi Jnum | J:279512 |
| Mgi Id | MGI:6361065 | Doi | 10.1073/pnas.1901056116 |
| Citation | Shen H, et al. (2019) Medullary thymic epithelial NF-kB-inducing kinase (NIK)/IKKalpha pathway shapes autoimmunity and liver and lung homeostasis in mice. Proc Natl Acad Sci U S A 116(38):19090-19097 |
| abstractText | Aberrant T cell development is a pivotal risk factor for autoimmune disease; however, the underlying molecular mechanism of T cell overactivation is poorly understood. Here, we identified NF-kappaB-inducing kinase (NIK) and IkB kinase alpha (IKKalpha) in thymic epithelial cells (TECs) as essential regulators of T cell development. Mouse TEC-specific ablation of either NIK or IKKalpha resulted in severe T cell-mediated inflammation, injury, and fibrosis in the liver and lung, leading to premature death within 18 d of age. NIK or IKKalpha deficiency abrogated medullary TEC development, and led to breakdown of central tolerance, production of autoreactive T cells, and fatal autoimmune destruction in the liver and lung. TEC-specific ablation of NIK or IKKalpha also impaired thymic T cell development from the double-negative through the double-positive stages and inhibited peripheral B cell development. These results unravel a hitherto unrecognized essential role of TEC-intrinsic NIK and IKKalpha pathways in autoimmunity and T cell-instigated chronic liver and lung diseases. |
