HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections
Summary: Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013445 |
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| author | Philipp Penninger Helena Brezovec Irina Tsymala Magdalena Teufl Trinh Phan-Canh Tamires Bitencourt Marie Brinkmann Walter Glaser Wilfried Ellmeier Michael Bonelli Karl Kuchler |
| author_facet | Philipp Penninger Helena Brezovec Irina Tsymala Magdalena Teufl Trinh Phan-Canh Tamires Bitencourt Marie Brinkmann Walter Glaser Wilfried Ellmeier Michael Bonelli Karl Kuchler |
| author_sort | Philipp Penninger |
| collection | DOAJ |
| description | Summary: Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor β receptor 2 (TGF-βRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo. Consequently, animals harboring excess Th17-polarized HDCA1-deficient CD4+ T cells develop increased kidney pathology upon invasive Candida albicans infection. Importantly, pharmacological inhibition of class I HDACs similarly increased IL-17A release by both mouse and human CD4+ T cells. Collectively, this work shows that HDAC1 controls T cell polarization, thus playing a critical role in the antifungal immune defense and infection outcomes. |
| format | Article |
| id | doaj-art-f28f3f111aae4ea7a61d8ea5f2b710a6 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-f28f3f111aae4ea7a61d8ea5f2b710a62025-08-20T02:22:34ZengElsevierCell Reports2211-12472024-12-01431211499310.1016/j.celrep.2024.114993HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infectionsPhilipp Penninger0Helena Brezovec1Irina Tsymala2Magdalena Teufl3Trinh Phan-Canh4Tamires Bitencourt5Marie Brinkmann6Walter Glaser7Wilfried Ellmeier8Michael Bonelli9Karl Kuchler10Max Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; CCRI – St. Anna Children's Cancer Research Institute, Vienna, AustriaMedical University of Vienna, Division of Rheumatology, Department of Internal Medicine III, 1090 Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, AustriaMedical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, 1090 Vienna, AustriaMedical University of Vienna, Division of Rheumatology, Department of Internal Medicine III, 1090 Vienna, AustriaMax Perutz Labs, Vienna BioCenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9, 1030, Vienna, Austria; Corresponding authorSummary: Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor β receptor 2 (TGF-βRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo. Consequently, animals harboring excess Th17-polarized HDCA1-deficient CD4+ T cells develop increased kidney pathology upon invasive Candida albicans infection. Importantly, pharmacological inhibition of class I HDACs similarly increased IL-17A release by both mouse and human CD4+ T cells. Collectively, this work shows that HDAC1 controls T cell polarization, thus playing a critical role in the antifungal immune defense and infection outcomes.http://www.sciencedirect.com/science/article/pii/S2211124724013445CP: Immunology |
| spellingShingle | Philipp Penninger Helena Brezovec Irina Tsymala Magdalena Teufl Trinh Phan-Canh Tamires Bitencourt Marie Brinkmann Walter Glaser Wilfried Ellmeier Michael Bonelli Karl Kuchler HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections Cell Reports CP: Immunology |
| title | HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections |
| title_full | HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections |
| title_fullStr | HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections |
| title_full_unstemmed | HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections |
| title_short | HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections |
| title_sort | hdac1 fine tunes th17 polarization in vivo to restrain tissue damage in fungal infections |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724013445 |
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