Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29980684.
- Also identified by DOI 10.1038/s41467-018-05095-7 and PMC identifier 6035278.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-γ-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-γ expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-γ production, but also the protective function of iNKT cells in arthritis.
Medical subject headings
- Arthritis
- Cell Differentiation
- Mutation
- Natural Killer T-Cells
- Thymus Gland
- ZAP-70 Protein-Tyrosine Kinase