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RASA3 inhibits Th1 differentiation and attenuates inflammatory immune response by restricting the HCK kinase

GSE313543 Mus musculus Expression profiling by high throughput sequencing 24 samples 2026/07/05 GPL24247
Summary
Type I immunity is marked by IFN-γ, with Th1 cells as a key subset; however, intrinsic negative regulators of Th1 remain poorly defined. We identified RASA3 as such a regulator, whose expression declines during Th1 differentiation. T cell-specific RASA3 knockout enhances Th1 differentiation and exacerbates allergic contact dermatitis. Mechanistically, RASA3 inhibits Hck mRNA translation via RPL36A. HCK then phosphorylates STAT4 at Y693, driving STAT4 dimerization, nuclear entry, and IFN-γ expression. This RASA3–HCK–STAT4 axis reveals a novel mechanism for Th1 negative regulation and offers potential therapeutic targets.
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