| First Author | Seo W | Year | 2026 |
| Journal | Life Sci Alliance | Volume | 9 |
| Issue | 10 | PubMed ID | 42448570 |
| Mgi Jnum | J:390186 | Mgi Id | MGI:8386716 |
| Doi | 10.26508/lsa.202603763 | Citation | Seo W, et al. (2026) SATB1 preserves CD4(+) T-cell fidelity and establishes Treg function in antitumor immunity. Life Sci Alliance 9(10) |
| abstractText | The genome organizer special AT-rich sequence binding protein 1 (SATB1) is critical for the development of T lymphocyte subsets by regulating Foxp3 and Pdcd1 expression. However, its physiological role in mature peripheral T cells has remained obscured by the severe developmental defects caused by early-stage gene knockout models. Here, we used a Thpok-cre driver to specifically delete Satb1 after CD4 lineage commitment. We demonstrate that SATB1 is continuously required to suppress Foxp3 expression in conventional CD4(+) T cells; however, this aberrant derepression does not confer Treg suppressive activity. In contrast, FoxP3(+)CD25(+) Tregs isolated from SATB1-deficient mice exhibit functional defects in immune suppressive function. Although SATB1 deletion does not cause severe global defects in the Treg transcriptome, it disrupts essential FoxP3-mediated gene regulation, resulting in a targeted failure to silence transcripts detrimental to Treg fitness. Physiologically, this Treg-specific functional defect significantly enhances antitumor immunity in a melanoma model. Our findings reveal a dual requirement for SATB1, preserving lineage fidelity by repressing Foxp3 in conventional T cells, while enforcing foundational programming required for Treg suppressive function. |
