Profound Treg perturbations correlate with COVID-19 severity
Profound Treg perturbations correlate with COVID-19 severity
ABSTRACT The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcome. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.
Chowdhary Kaitavjeet、Manickas-Hill Zachary、Piechocka-Trocha Alicja、Worrall Daniel P.、Hall Kathryn E.、Walker Bruce D.、Leon Juliette、Yang Liang、Michelson Daniel A.、Magnuson Angela、Ghebremichael Musie、Galv¨￠n-Pe?a Silvia、Yu Xu G.、Li Jonathan、Mathis Diane、Vijaykumar Brinda、Benoist Christophe、MGH COVID-19 Collection & Processing Team
Department of Immunology, Harvard Medical SchoolMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardMassachusetts Consortium on Pathogen Readiness||Department of Medicine, Massachusetts General HospitalMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and Harvard||Howard Hughes Medical Institute, Center for the AIDS Programme of Research in South AfricaDepartment of Immunology, Harvard Medical School||INSERM UMR 1163, University of Paris, Imagine InstituteDepartment of Immunology, Harvard Medical SchoolDepartment of Immunology, Harvard Medical SchoolDepartment of Immunology, Harvard Medical SchoolMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardDepartment of Immunology, Harvard Medical SchoolMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardMassachusetts Consortium on Pathogen Readiness||Ragon Institute of MGH, MIT and HarvardDepartment of Immunology, Harvard Medical SchoolDepartment of Immunology, Harvard Medical SchoolDepartment of Immunology, Harvard Medical School
医药卫生理论医学研究方法基础医学
Chowdhary Kaitavjeet,Manickas-Hill Zachary,Piechocka-Trocha Alicja,Worrall Daniel P.,Hall Kathryn E.,Walker Bruce D.,Leon Juliette,Yang Liang,Michelson Daniel A.,Magnuson Angela,Ghebremichael Musie,Galv¨￠n-Pe?a Silvia,Yu Xu G.,Li Jonathan,Mathis Diane,Vijaykumar Brinda,Benoist Christophe,MGH COVID-19 Collection & Processing Team.Profound Treg perturbations correlate with COVID-19 severity[EB/OL].(2025-03-28)[2025-06-14].https://www.biorxiv.org/content/10.1101/2020.12.11.416180.点此复制
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