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TYK2 signaling promotes the development of autoreactive CD8 + cytotoxic T lymphocytes and type 1 diabetes.
- Source :
-
Nature communications [Nat Commun] 2024 Feb 13; Vol. 15 (1), pp. 1337. Date of Electronic Publication: 2024 Feb 13. - Publication Year :
- 2024
-
Abstract
- 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 <superscript>+</superscript> 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 <superscript>+</superscript> T-BET <superscript>+</superscript> cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8 <superscript>+</superscript> T cells and the CD8 <superscript>+</superscript> resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in β-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET <superscript>+</superscript> CTLs, inflammation in β-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.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38351043
- Full Text :
- https://doi.org/10.1038/s41467-024-45573-9