| First Author | Viret C | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 5 | Pages | 1810-21 |
| PubMed ID | 21505262 | Mgi Jnum | J:173941 |
| Mgi Id | MGI:5050580 | Doi | 10.1172/JCI43314 |
| Citation | Viret C, et al. (2011) Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice. J Clin Invest 121(5):1810-21 |
| abstractText | Type 1 diabetes is a chronic autoimmune disease in which genetic predispositions affect the immune system, leading to a loss of T cell tolerance to beta cells and consequent T cell-mediated destruction of insulin-producing islet cells. Genetic studies have suggested that PRSS16 is linked to a diabetes susceptibility locus of the extended HLA class I region in humans. PRSS16 encodes what we believe to be a novel protease, thymus-specific serine protease (TSSP), which shows predominant expression in thymic epithelial cells and is suspected to have a restricted role in the class II presentation pathway. Consistently, Tssp is necessary for the intrathymic selection of few class II-restricted T cell receptor specificities in B6 mice. To directly assess the role of Tssp in autoimmune diabetes, we generated Tssp-deficient (Tssp degrees ) NOD mice. While remaining immunocompetent, Tssp degrees NOD mice were protected from diabetes and severe insulitis. Diabetes resistance of Tssp degrees NOD mice was a property of the CD4 T cell compartment that is acquired during thymic selection and correlated with an impaired selection of CD4 T cells specific for islet antigens. Hence, in the NOD mouse, Tssp is a critical regulator of diabetes development through the selection of the autoreactive CD4 T cell repertoire. |
