Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology
Summary: Regulatory T (Treg) cells are critical for maintaining peripheral tolerance and preventing autoimmunity. Treg cell depletion or dysfunction results in fatal multiorgan inflammation linked to unrestrained effector T cell expansion. Here, we combine in vivo gene targeting and fate-mapping wit...
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| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004139 |
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| author | Sara Costa-Pereira Margit Lanzinger Nicolás Núñez Juan Villar-Vesga Myrto Andreadou Francesco Prisco Philipp Häne Elsa Roussel Sinduya Krishnarajah Rachel Chanel Lindemann Laura Oberbichler Frederike Westermann André Fonseca Da Silva Virginia Cecconi Mirjam Pinzger Sonia Tugues Sarah Mundt Melanie Greter Donatella De Feo Burkhard Becher |
| author_facet | Sara Costa-Pereira Margit Lanzinger Nicolás Núñez Juan Villar-Vesga Myrto Andreadou Francesco Prisco Philipp Häne Elsa Roussel Sinduya Krishnarajah Rachel Chanel Lindemann Laura Oberbichler Frederike Westermann André Fonseca Da Silva Virginia Cecconi Mirjam Pinzger Sonia Tugues Sarah Mundt Melanie Greter Donatella De Feo Burkhard Becher |
| author_sort | Sara Costa-Pereira |
| collection | DOAJ |
| description | Summary: Regulatory T (Treg) cells are critical for maintaining peripheral tolerance and preventing autoimmunity. Treg cell depletion or dysfunction results in fatal multiorgan inflammation linked to unrestrained effector T cell expansion. Here, we combine in vivo gene targeting and fate-mapping with high-dimensional cytometry to identify Treg cells’ steady-state function and suppressive mechanisms that prevent autoimmune inflammation and dissect the T helper (TH) cell-derived cytokines and responding cells executing tissue damage upon global loss of peripheral tolerance. We unveil that type 1 cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)γ, but not interleukin (IL)-17A, direct the ensuing immunopathology and mortality. GM-CSF orchestrates tissue invasion by monocytes and granulocytes and enhances their reactive oxygen species production and phagocytic capability. IL-2 modulation by Treg cells is crucial in restraining pathogenic GM-CSF-producing TH cells. Our study highlights the critical role of Treg cells and IL-2 signaling in controlling GM-CSF-producing TH cells and type 1 responses to curb phagocyte-mediated tissue destruction. |
| format | Article |
| id | doaj-art-c6c0f4f4ad2a44a4a9505efd567c68c8 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-c6c0f4f4ad2a44a4a9505efd567c68c82025-08-20T01:48:46ZengElsevierCell Reports2211-12472025-05-0144511564210.1016/j.celrep.2025.115642Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathologySara Costa-Pereira0Margit Lanzinger1Nicolás Núñez2Juan Villar-Vesga3Myrto Andreadou4Francesco Prisco5Philipp Häne6Elsa Roussel7Sinduya Krishnarajah8Rachel Chanel Lindemann9Laura Oberbichler10Frederike Westermann11André Fonseca Da Silva12Virginia Cecconi13Mirjam Pinzger14Sonia Tugues15Sarah Mundt16Melanie Greter17Donatella De Feo18Burkhard Becher19Institute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland; Faculty of Chemical Sciences, National University of Córdoba, X5000 Córdoba, ArgentinaInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland; Corresponding authorSummary: Regulatory T (Treg) cells are critical for maintaining peripheral tolerance and preventing autoimmunity. Treg cell depletion or dysfunction results in fatal multiorgan inflammation linked to unrestrained effector T cell expansion. Here, we combine in vivo gene targeting and fate-mapping with high-dimensional cytometry to identify Treg cells’ steady-state function and suppressive mechanisms that prevent autoimmune inflammation and dissect the T helper (TH) cell-derived cytokines and responding cells executing tissue damage upon global loss of peripheral tolerance. We unveil that type 1 cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)γ, but not interleukin (IL)-17A, direct the ensuing immunopathology and mortality. GM-CSF orchestrates tissue invasion by monocytes and granulocytes and enhances their reactive oxygen species production and phagocytic capability. IL-2 modulation by Treg cells is crucial in restraining pathogenic GM-CSF-producing TH cells. Our study highlights the critical role of Treg cells and IL-2 signaling in controlling GM-CSF-producing TH cells and type 1 responses to curb phagocyte-mediated tissue destruction.http://www.sciencedirect.com/science/article/pii/S2211124725004139CP: Immunology |
| spellingShingle | Sara Costa-Pereira Margit Lanzinger Nicolás Núñez Juan Villar-Vesga Myrto Andreadou Francesco Prisco Philipp Häne Elsa Roussel Sinduya Krishnarajah Rachel Chanel Lindemann Laura Oberbichler Frederike Westermann André Fonseca Da Silva Virginia Cecconi Mirjam Pinzger Sonia Tugues Sarah Mundt Melanie Greter Donatella De Feo Burkhard Becher Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology Cell Reports CP: Immunology |
| title | Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology |
| title_full | Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology |
| title_fullStr | Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology |
| title_full_unstemmed | Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology |
| title_short | Regulatory T cells suppress GM-CSF-producing T helper cells via IL-2 modulation to restrain immunopathology |
| title_sort | regulatory t cells suppress gm csf producing t helper cells via il 2 modulation to restrain immunopathology |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004139 |
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