ArticleEMBO reports2026
SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.
Article in EMBO reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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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