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The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [ATAC-Seq]

GSE308747 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2026/02/01 Platform GPL21103
Summary
Aberrant activated T cell infiltration is a key driver of autoimmune pathogenesis, highlighting the therapeutic potential of inhibiting T cell migration. However, the regulatory mechanisms governing tissue ingress of antigen-specific T cells remain elusive. Here, we report that SUB1, a transcription factor upregulated in CD4+ T cells from patients with autoimmune disorders, is regulated by the TCR–IRF4 axis. SUB1 deficiency diminished DOCK2 expression by 50%, impairing Rac-dependent actin polymerization and T cell migration, and consequently suppressed the onset of experimental autoimmune encephalomyelitis (EAE). Mechanistically, SUB1 promotes chromatin accessibility at the Junb and Dock2 loci via liquid–liquid phase separation (LLPS), facilitating biomolecular condensate formation. Furthermore, SUB1 directly activates Junb transcription and cooperates with JUNB to enhance Dock2 expression. Our results identify SUB1 as a critical regulator of antigen-specific CD4+ T cell migration and propose it as a promising therapeutic target for autoimmune diseases.
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Also filed as BioProject PRJNA1332637 and SRA study SRP624778. Searching any of these in the dataset finder brings you back here.

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