| First Author | Mine K | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 1337 |
| PubMed ID | 38351043 | Mgi Jnum | J:351985 |
| Mgi Id | MGI:7594898 | Doi | 10.1038/s41467-024-45573-9 |
| Citation | Mine K, et al. (2024) TYK2 signaling promotes the development of autoreactive CD8(+) cytotoxic T lymphocytes and type 1 diabetes. Nat Commun 15(1):1337 |
| abstractText | Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8(+) T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8(+) T-BET(+) cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8(+) T cells and the CD8(+) resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in beta-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET(+) CTLs, inflammation in beta-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D. |
