Downregulation of Satb1 is required to prevent autoimmunity by maintaining Tfh homeostasis

Mehrnoush Hadaddzadeh Shakiba; Maren Köhne; Tarek Elmzzahi; Luisa Bach; Doaa Hamada; Leonie Heyden; Anna F. Lindemann; Jannis Bastian Spintge; Aleksej Frolov; Yuanfang Li; Lisa Holsten; Marlene Gottschalk; Celia Kho; Darya Malko; Collins Osei-Sarpong; Rebekka Scholz; Xiaoxiao Cheng; Anna Neubauer; Jonas Schulte-Schrepping; Yinshui Chang; Lorenzo Bonaguro; Heike Weighardt; T Ulas; Joachim Ludwig Schultze; FT Wunderlich; Elena De Domenico; Axel Kallies; Zeinab Abdullah; Dirk Baumjohann; Marc Beyer

doi:10.64898/2026.02.03.703482

ImmunologybioRxivFeb 5, 2026

Preprint

Downregulation of Satb1 is required to prevent autoimmunity by maintaining Tfh homeostasis

Mehrnoush Hadaddzadeh Shakiba iD, Maren Köhne iD, Tarek Elmzzahi iD, Luisa Bach iD, Doaa Hamada iD, Leonie Heyden iD, Anna F. Lindemann, Jannis Bastian Spintge iD, Aleksej Frolov, Yuanfang Li, Lisa Holsten iD, Marlene Gottschalk iD, Celia Kho iD, Darya Malko iD, Collins Osei-Sarpong iD, Rebekka Scholz iD, Xiaoxiao Cheng iD, Anna Neubauer iD, Jonas Schulte-Schrepping iD, Yinshui Chang iD, Lorenzo Bonaguro iD, Heike Weighardt iD, T Ulas, Joachim Ludwig Schultze iD, FT Wunderlich iD, , Marc Beyer iD

Abstract

T follicular helper (Tfh) cells are a specialized subset of CD4 T cells that localize to germinal centers (GC), where they provide critical help to B cells through the delivery of IL-21 and other cytokines. Here, we demonstrate that the tight control of the chromatin remodeler Special AT-rich sequence-binding protein 1 (Satb1) is key for this process, as overexpression of Satb1 drives lymphoproliferation and expansion of the T cell and B cell compartments in secondary lymphoid organs. Specifically, Satb1 overexpression induces a pronounced shift towards Tfh cell differentiation and increased GC formation accompanied by an increase in non-classed switched GC B cells and auto-antibody secretion. These findings highlight the importance of the precise regulation of Satb1 in fine-tuning CD4 T cells and B cells responses and suggest a potential role for dysregulation of Satb1 in the pathogenesis of autoimmune disease such as systemic lupus erythematodes (SLE).

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