Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression
T helper (T<sub>H</sub>)17 cells are crucial for host defense in barrier organs, and their altered functionality can disrupt tissue homeostasis, increasing the risk of autoimmune diseases. Thus, it is essential to understand the mechanisms controlling T<sub>H</sub>17 differentiation to develop strategies influencing their role in diseases. Here, we identified Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for T<sub>H</sub>17 development. Satb1 is highly expressed in T<sub>H</sub>17 cells, and loss of Satb1 prevents the differentiation of T<sub>H</sub>17 cells. Consequently, expression of Satb1 in CD4<sup>+</sup> T cells is required for the formation of T<sub>H</sub>17-driven autoimmune diseases. Mechanistically, Satb1 mediates T<sub>H</sub>17 development through regulating accessibility of the Il2 gene locus and thereby preventing interleukin (IL)-2 signaling early during T<sub>H</sub>17 differentiation. Hence, suppression of IL-2 expression by Satb1 during T<sub>H</sub>17 formation is pivotal, suggesting that Satb1 could serve as a novel therapeutic target for treating autoimmune diseases driven by T<sub>H</sub>17 cells.
Authors
- Mehrnoush Hadaddzadeh Shakiba (ORCID: https://orcid.org/0000-0001-5851-685X)
- Jannis Wißfeld (ORCID: https://orcid.org/0000-0003-0993-3109)
- Rebekka Scholz (ORCID: https://orcid.org/0000-0003-2077-0718)
- Claudia Wickenhauser (ORCID: https://orcid.org/0000-0002-1807-5575)
- Lisa Holsten (ORCID: https://orcid.org/0000-0001-6238-1273)
- Xiaoxiao Cheng
- Timothy Sadlon (ORCID: https://orcid.org/0000-0002-4821-2462)
- Judith Alferink (ORCID: https://orcid.org/0000-0002-3251-6584)
- Marc Beyer (ORCID: https://orcid.org/0000-0001-9704-148X)
- Stefan Paulusch
- Maren Köhne
- Collins Osei-Sarpong (ORCID: https://orcid.org/0000-0002-1093-5147)
- Tarek Elmzzahi (ORCID: https://orcid.org/0000-0003-1168-8114)
- Lisa Schmidleithner (ORCID: https://orcid.org/0009-0001-0852-5835)
- Elena De Domenico (ORCID: https://orcid.org/0000-0003-0336-8284)
- Hannes Renken
- Tanja Kuhlmann (ORCID: https://orcid.org/0000-0002-0174-5042)
- Eva Christina Schulte (ORCID: https://orcid.org/0000-0003-3105-5672)
- Kristian Händler (ORCID: https://orcid.org/0000-0001-5273-5277)
- Svenja Bourry
- Caterina Carraro (ORCID: https://orcid.org/0000-0002-3039-4675)
- Matthias Geyer (ORCID: https://orcid.org/0000-0002-7718-5002)
- F. Thomas Wunderlich (ORCID: https://orcid.org/0000-0002-9209-3501)
- Joachim L. Schultze (ORCID: https://orcid.org/0000-0003-2812-9853)
- Lorenzo Bonaguro (ORCID: https://orcid.org/0000-0001-9675-7208)
- Thorsten Buch (ORCID: https://orcid.org/0000-0002-2236-9074)
- Simon C. Barry (ORCID: https://orcid.org/0000-0002-0597-7609)
- Ann-Kathrin Baumgart
- Doaa Hamada (ORCID: https://orcid.org/0009-0000-6688-7175)
- Yuanfang Li (ORCID: https://orcid.org/0000-0002-2646-3260)
- A. N. FROLOV (ORCID: https://orcid.org/0000-0002-4406-1206)
- Yasser Thabet
- Daniel Sommer
Institutions
- University of Bonn (DE)
- Johannes Gutenberg University Mainz (DE)
- University of Zurich (CH)
- University of Münster (DE)
- University Hospital Bonn (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital Münster (DE)
- Peter Doherty Institute (AU)
- Max Planck Institute for Metabolism Research (DE)
- Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz (DE)
- The University of Adelaide (AU)
- FH Münster University of Applied Sciences (DE)
- Martin Luther University Halle-Wittenberg (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1016/j.celrep.2025.115866
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- National Science Foundation
- Schlumberger Foundation
- European Commission
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- H2020 European Research Council
- H2020 Health