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

Kolb, S.; Diekmann, L.; Lochert, E. D.; Warmuth, L.; Ritter, J.; Weber, M.; Hoffmann, M.; List, M.; Kotlarz, D.; Serr, I.; Daniel, C.; Busch, D. H.; Schmidl, C.; Schumann, K.

doi:10.64898/2026.02.13.705474

bioRxiv · 10.64898/2026.02.13.705474

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

Kolb, S.·Diekmann, L.·Lochert, E. D.·Warmuth, L.·Ritter, J.·Weber, M.·Hoffmann, M.·List, M.·Kotlarz, D.·Serr, I.·Daniel, C.·Busch, D. H.·Schmidl, C.·Schumann, K.

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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 SATB1s potential as a target for T cell engineering, are poorly understood. We describe SATB1-regulated gene signatures as largely subset-specific, with broader effects on Treg cells. Despite of the distinct gene-regulatory patterns, we observe overarching dysregulated cytokine and JAK-STAT signaling after SATB1 ablation. Functionally, SATB1 KO reduces human Treg cell suppressive capacities but boosts tumor clearance via CD4 CAR T cells in a preclinical, humanized mouse model. Together, Treg destabilization and simultaneous increased activation of CD4 CAR T cells by SATB1 modulation may be an interesting strategy to boost the efficiency of CAR T cell therapies.

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Kolb, S., Diekmann, L., Lochert, E. D., Warmuth, L., Ritter, J., Weber, M., Hoffmann, M., List, M., Kotlarz, D., Serr, I., Daniel, C., Busch, D. H., Schmidl, C., Schumann, K.. 2026-02-16. SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells. https://doi.org/10.64898/2026.02.13.705474

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