| First Author | Li X | Year | 2026 |
| Journal | Immunity | Volume | 59 |
| Issue | 1 | Pages | 98-115.e8 |
| PubMed ID | 41371223 | Mgi Jnum | J:385846 |
| Mgi Id | MGI:8277536 | Doi | 10.1016/j.immuni.2025.11.009 |
| Citation | Li X, et al. (2026) The TCR-SUB1-DOCK2 axis promotes autoimmunity by driving pathogenic CD4(+) T cell tissue infiltration. Immunity 59(1):98-115.e8 |
| abstractText | Aberrant tissue infiltration by activated CD4(+) T cells is a central driver of autoimmunity, yet the molecular checkpoints governing antigen-specific T cell ingress remain poorly defined. We found that the transcription factor SUB1 was selectively upregulated in CD4(+) T cells from individuals with autoimmune diseases. SUB1 expression was induced by the T cell receptor (TCR)-interferon regulatory factor 4 (IRF4) transcription factor axis. Conditional deletion of Sub1 in T cells reduced the expression of migration regulator dedicator of cytokinesis 2 (DOCK2), inhibited Rac-dependent actin polymerization and T cell motility, and prevented the onset of experimental autoimmune encephalomyelitis. Mechanistically, SUB1 underwent liquid-liquid phase separation to form biomolecular condensates that opened chromatin at the Junb and Dock2 loci. It then directly trans-activated Junb transcription and partnered with JUNB to amplify Dock2 transcription. Therefore, SUB1 is a critical gatekeeper of pathogenic T cell trafficking, and by linking TCR signaling to cytoskeletal remodeling, the TCR-SUB1-DOCK2 axis emerges as a tractable, migration-focused therapeutic target in autoimmune disorders. |
