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Article Abstract
IL-17-producing γδ T (Tγδ17) cells are innate-like mediators of intestinal barrier immunity. While Th17 cell and ILC3 plasticity have been extensively studied, the mechanisms governing Tγδ17 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 Tγδ17 cell plasticity. During homeostasis, Tγδ17 cell effector identity was stable across tissues, including for intestinal T-bet Tγδ17 cells that restrained IFNγ production. However, infection induced intestinal Vγ6 Tγδ17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORγt downregulation. Multiome analysis revealed a trajectory along Vγ6 Tγδ17 effector conversion, with TIM-3 marking ex-Tγδ17 cells with enhanced type 1 functionality. Lastly, we characterized and validated a critical AP-1 regulatory axis centered around JunB and Fosl2 that controls Vγ6 Tγδ17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507935 | PMC |
| http://dx.doi.org/10.1101/2024.10.15.618522 | DOI Listing |
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