Regulatory T-cells are central hubs for age-, sex- and severity-associated cellular networks during COVID-19
Regulatory T-cells are central hubs for age-, sex- and severity-associated cellular networks during COVID-19
Abstract Using single-cell proteomics by mass cytometry, we investigate changes to a broad selection of over 10,000,000 immune cells in a cohort of moderate, severe, and critical Japanese COVID-19 patients and healthy controls with a particular focus on regulatory T-cells (Tregs). We find significant disruption within all compartments of the immune system and the emergence of atypical CTLA-4high CD4 T-cells and proliferating HLA-DRlowCD38high Tregs associated with critical patients. We also observed disrupted regulation of humoral immunity in COVID-19, with a loss of circulating T follicular regulatory T cells (Tfr) and altered T follicular helper (Tfh)/Tfr and plasma cell/Tfr ratios, all of which are significantly lower in male patients. Shifting ratios of CXCR4 and CXCR5 expression in B-cells provides further evidence of an autoimmune phenotype and dysregulated humoral immunity. These results suggest that Tregs are central to the changing cellular networks of a wide range of cells in COVID-19 and that sex specific differences to the balance of Tfr, Tfh and plasma cells may have important implications for the specificity of the humoral immune response to SARS-CoV-2.
Takeda Yoshito、Sakaguchi Shimon、Wing James B.、Kumanogoh Atsushi、Edahiro Ryuya、Yamaguchi Yuta、Murakami Teruaki、Morita Takayoshi、Kato Yasuhiro、Hirata Haruhiko、Okuzaki Daisuke、Okada Yukinori、S?ndergaard Jonas N.、Tulyeu Janyerkye、Shira Yuya
Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineLaboratory of Experimental Immunology Osaka University||Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto UniversityHuman Immunology Team, Center for Infectious Diseases Education and Research (CiDER), Osaka University||Laboratory of Human Immunology (Single Cell Immunology) Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University||Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University||CiDER, Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Statistical Genetics, Osaka University Graduate School of MedicineDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineLaboratory of Human Immunology (Single Cell Genomics) Osaka University||Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University||Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University||CiDER, Osaka UniversityDepartment of Statistical Genetics, Osaka University Graduate School of Medicine||Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University||CiDER, Osaka University||Laboratory of Statistical Immunology. WPI-IFReC, Osaka University||Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||Laboratory for Systems Genetics, RIKEN Center for Integrative Medical SciencesHuman Immunology Team, Center for Infectious Diseases Education and Research (CiDER), Osaka UniversityHuman Immunology Team, Center for Infectious Diseases Education and Research (CiDER), Osaka UniversityDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine||Department of Statistical Genetics, Osaka University Graduate School of Medicine
基础医学生物科学研究方法、生物科学研究技术
Takeda Yoshito,Sakaguchi Shimon,Wing James B.,Kumanogoh Atsushi,Edahiro Ryuya,Yamaguchi Yuta,Murakami Teruaki,Morita Takayoshi,Kato Yasuhiro,Hirata Haruhiko,Okuzaki Daisuke,Okada Yukinori,S?ndergaard Jonas N.,Tulyeu Janyerkye,Shira Yuya.Regulatory T-cells are central hubs for age-, sex- and severity-associated cellular networks during COVID-19[EB/OL].(2025-03-28)[2025-05-05].https://www.medrxiv.org/content/10.1101/2022.01.06.22268711.点此复制
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