TY  - JOUR
AU  - Köhne, Maren
AU  - Shakiba, Mehrnoush Hadaddzadeh
AU  - Schmidleithner, Lisa
AU  - Schulte-Schrepping, Jonas
AU  - Scholz, Rebekka
AU  - Elmzzahi, Tarek
AU  - Sommer, Daniel
AU  - Li, Yuanfang
AU  - Carraro, Caterina
AU  - De Domenico, Elena
AU  - Wißfeld, Jannis
AU  - Händler, Kristian
AU  - Hamada, Doaa
AU  - Frolov, Aleksej
AU  - Cheng, Xiaoxiao
AU  - Baumgart, Ann-Kathrin
AU  - Holsten, Lisa
AU  - Osei-Sarpong, Collins
AU  - Bourry, Svenja
AU  - Thabet, Yasser
AU  - Renken, Hannes
AU  - Paulusch, Stefan
AU  - Sadlon, Timothy
AU  - Buch, Thorsten
AU  - Wunderlich, F Thomas
AU  - Wickenhauser, Claudia
AU  - Alferink, Judith
AU  - Kuhlmann, Tanja
AU  - Geyer, Matthias
AU  - Bonaguro, Lorenzo
AU  - Barry, Simon C
AU  - Schultze, Joachim L
AU  - Beyer, Marc D
TI  - Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression.
JO  - Cell reports
VL  - 44
IS  - 7
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DZNE-2025-00764
SP  - 115866
PY  - 2025
AB  - T helper (TH)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 TH17 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 TH17 development. Satb1 is highly expressed in TH17 cells, and loss of Satb1 prevents the differentiation of TH17 cells. Consequently, expression of Satb1 in CD4+ T cells is required for the formation of TH17-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 development through regulating accessibility of the Il2 gene locus and thereby preventing interleukin (IL)-2 signaling early during TH17 differentiation. Hence, suppression of IL-2 expression by Satb1 during TH17 formation is pivotal, suggesting that Satb1 could serve as a novel therapeutic target for treating autoimmune diseases driven by TH17 cells.
KW  - CD4(+) T cell differentiation (Other)
KW  - CP: Immunology (Other)
KW  - EAE (Other)
KW  - IL-2 (Other)
KW  - Satb1 (Other)
KW  - T(H)17 cells (Other)
KW  - autoimmune disease (Other)
KW  - colitis (Other)
KW  - scRNA-seq (Other)
KW  - single-cell MultiOMICs (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40531625
DO  - DOI:10.1016/j.celrep.2025.115866
UR  - https://pub.dzne.de/record/279433
ER  -