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

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

EMBO Rep., DOI: 10.1038/s44319-026-00812-6 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Transcription Factor ; Chromatin ; Cytokine ; T Cell ; Gata3 ; Gene ; Cell ; Regulatory T Cell
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Publisher Springer
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Research Unit Type 1 Diabetes Immunology (TDI)
Grants Deutsche Krebshilfe (German Cancer Aid)
Else Kroener-Fresenius Foundation
Deutsche Forschungsgemeinschaft (DFG)