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Restriction of innate Tgd17 cell plasticity by an AP-1 regulatory axis [CUT&Run]

GSE290580 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2025/05/27 Platform GPL32159
Summary
IL-17-producing gd T (Tgd17) cells are innate-like mediators of intestinal barrier immunity. While Th17 cell and ILC3 plasticity have been extensively studied, the mechanisms governing Tgd17 cell effector flexibility remain undefined. Here, we combined type 3 fate-mapping with single cell ATAC/RNA-seq multiome profiling to define the cellular features and regulatory networks underlying Tgd17 cell plasticity. During homeostasis, Tgd17 cell effector identity was stable across tissues, including for intestinal T-bet+ Tgd17 cells that restrained IFNg production. However, S. typhimurium infection induced intestinal Vg6+ Tgd17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORgt downregulation. Multiome analysis revealed a trajectory along Vg6+ Tgd17 effector conversion, with TIM-3 marking ex-Tgd17 cells with enhanced type 1 functionality. Lastly, we characterized and validated a critical AP-1 regulatory axis centered around JunB and Fosl2 that controls Vg6+ Tgd17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion.
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Direct links to NCBI, no account and no request form: the whole study as GSE290580_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1228659 and SRA study SRP566527. Searching any of these in the dataset finder brings you back here.

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