SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells
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.
Authors
- Michael Weber (ORCID: https://orcid.org/0000-0001-5647-6217)
- Christian Schmidl (ORCID: https://orcid.org/0000-0002-0522-202X)
- Linda Warmuth (ORCID: https://orcid.org/0000-0003-3324-7731)
- Isabelle Serr (ORCID: https://orcid.org/0000-0001-9277-9055)
- Kathrin Schumann
- Markus Hoffmann (ORCID: https://orcid.org/0000-0002-1920-288X)
- Daniel Kotlarz (ORCID: https://orcid.org/0000-0002-4576-6769)
- Saskia Kolb
- Carolin Daniel (ORCID: https://orcid.org/0000-0003-4698-7069)
- Dirk Hans Busch (ORCID: https://orcid.org/0000-0001-8713-093X)
- Gunter Schmidtke
- Leonie Diekmann
- Markus List (ORCID: https://orcid.org/0000-0002-0941-4168)
- Julia Ritter
- Elizabeth E Lochert
Institutions
- Georgetown University (US)
- University of Konstanz (DE)
- Georgetown University Medical Center (US)
- Helmholtz Zentrum München (DE)
- LMU Klinikum (DE)
- Leibniz Association (DE)
- German Center for Pediatric and Adolescent Rheumatology (DE)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- German Center for Infection Research (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Deutsches Herzzentrum München (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- EMBO Reports
- Published
- 2026-06-12
- DOI
- https://doi.org/10.1038/s44319-026-00812-6
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Georgetown University
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Universität Konstanz
- National Institute of Diabetes and Digestive and Kidney Diseases