Loss of DUSP2-RPA signaling enhances virtual memory T cell-mediated innate-like antiviral immunity.

DUSP2 deficiency enhances CD8+ virtual memory T cell–mediated antiviral immunity and expands a highly activated CD44 super-high T VM subset with rapid, antigen-independent effector responses.

• Why it matters: The differentiation and antiviral regulation of antigen-inexperienced virtual memory CD8+ T cells is unclear, limiting understanding of how innate-like antiviral programs are controlled.
• What they did: Using an autoantibody-based screening strategy, the study identifies DUSP2 as a regulator; DUSP2 interacts with the replication protein A (RPA) complex to control RPA2 phosphorylation and chromatin association.
• The result: Disrupting the DUSP2-RPA axis increases R-loop accumulation and chromatin accessibility, activating Eomesodermin (EOMES)-linked transcription and promoting T VM differentiation; T cell–specific RPA1 deletion phenocopies spontaneous T VM accumulation and rapid effector-like responses after viral challenge.

AI summary of the abstract · may contain errors · not medical advice · read the paper.