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Publication : SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.

First Author  Kolb S Year  2026
Journal  EMBO Rep Volume  27
Issue  14 Pages  4029-4053
PubMed ID  42286212 Mgi Jnum  J:390432
Mgi Id  MGI:8395264 Doi  10.1038/s44319-026-00812-6
Citation  Kolb S, et al. (2026) SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells. EMBO Rep 27(14):4029-4053
abstractText  The chromatin organizer SATB1 is indispensable for thymic regulatory T cell (Treg cell) development and T helper cell induction. Several gene loci have been described to be SATB1-controlled, including the transcription factor GATA3 and the cytokine loci IL-4 and IL-17. However, the global effects of SATB1 on fully differentiated human CD4 conventional T cells (Tconv cells) and Treg cells, and thus the potential of SATB1 as a target for T-cell engineering, are poorly understood. Here, we describe SATB1-regulated gene signatures as largely subset-specific, with broader effects on Treg cells. Despite distinct gene-regulatory patterns, we observe overarching dysregulated cytokine and JAK-STAT signaling after SATB1 ablation. Functionally, SATB1 KO reduces suppressive capacities of human Treg cells but boosts tumor clearance via CD4 CAR T cells in a preclinical, humanized mouse model. Taken together, Treg destabilization and simultaneous increased activation of CD4 CAR T cells by SATB1 modulation may be a strategy to boost the efficiency of CAR T cell therapies.
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