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

Shakiba, M. H.; Koehne, M.; Elmzzahi, T. E.; Bach, L.; Hamada, D.; Heyden, L.; Lindemann, A.; Spintge, J. B.; Frolov, A.; Li, Y.; Holsten, L.; Gottschalk, M.; Kho, C.; Malko, D.; Osei-Sarpong, C.; Scholz, R.; Cheng, X.; Neubauer, A.; Schulte-Schrepping, J.; Chang, Y.; Bonaguro, L.; Weighardt, H.; Ulas, T.; Schultze, J. L.; Wunderlich, F. T.; De Domenico, E.; Kallies, A.; Abdullah, Z.; Baumjohann, D.; Beyer, M. D.

doi:10.64898/2026.02.03.703482

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bioRxiv · 10.64898/2026.02.03.703482

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

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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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Shakiba, M. H., Koehne, M., Elmzzahi, T. E., Bach, L., Hamada, D., Heyden, L., Lindemann, A., Spintge, J. B., Frolov, A., Li, Y., Holsten, L., Gottschalk, M., Kho, C., Malko, D., Osei-Sarpong, C., Scholz, R., Cheng, X., Neubauer, A., Schulte-Schrepping, J., Chang, Y., Bonaguro, L., Weighardt, H., Ulas, T., Schultze, J. L., Wunderlich, F. T., De Domenico, E., Kallies, A., Abdullah, Z., Baumjohann, D., Beyer, M. D.. 2026-02-05. Downregulation of Satb1 is required to prevent autoimmunity by maintaining Tfh homeostasis. https://doi.org/10.64898/2026.02.03.703482

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