Immunity：王锋团队揭示自身免疫疾病发病新机制，并提出治疗新靶点

Core Viewpoint - The study identifies the TCR-SUB1-DOCK2 signaling axis as a crucial pathway linking TCR antigen recognition signals to CD4⁺ T cell tissue migration, providing new insights into the mechanisms of autoimmune diseases and potential therapeutic targets for immune intervention strategies [5]. Group 1: Research Findings - The research team discovered that the transcription factor SUB1 is selectively upregulated in CD4⁺ T cells from autoimmune disease patients, induced by the T cell receptor (TCR)-interferon regulatory factor-4 (IRF4) signaling axis [2]. - Conditional knockout of Sub1 in T cells reduces the expression of the cell division control factor DOCK2, inhibiting Rac-dependent actin polymerization and T cell motility, thereby preventing the onset of experimental autoimmune encephalomyelitis [2]. - SUB1 forms biomolecular condensates through liquid-liquid phase separation (LLPS), opening chromatin at the Junb and Dock2 gene loci, directly activating Junb transcription, and amplifying Dock2 transcription in collaboration with JUNB [2]. Group 2: Implications for Autoimmunity - The TCR-SUB1-DOCK2 signaling axis serves as a therapeutic target focused on the migration pathways of pathogenic T cells, linking TCR signaling to cytoskeletal reorganization [2]. - This research deepens the understanding of the pathogenesis of autoimmune diseases and provides a theoretical basis and potential targets for developing precise and safe immune intervention strategies [5].