GSE114555 Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70 [RNA-Seq]

Contributors : Meng Zhao ; Mattias N Svensson ; Koen Venken ; Ashu Sethi ; Shu Liang ; Isaac Engel ; Piotr Mydel ; Jeremy Day ; Dirk Elewaut ; Nunzio Bottini ; Mitchell KronenbergSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusVarious 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 lead to an increase of IFN-g-producing iNKT cells (NKT1 cells), suggesting NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. iNKT cells and therapeutic induction of IFN-g secretion by activating iNKT cells are protective in this model, but the representation of IFNg versus IL-17 secreting iNKT cells in the joint change in favor of IL-17 producers as disease worsened. NKT1 cells are also present in the synovial fluid of arthritis patients, where they could be beneficial. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFNg production, but also the protective function of iNKT cells in arthritis.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research