A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients-Reference-Cited by-同舟云学术

A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients

Published:2023-01-20 Issue:4 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Søndergaard Jonas Nørskov¹^ORCID,Tulyeu Janyerkye¹^ORCID,Edahiro Ryuya²³,Shirai Yuya²³,Yamaguchi Yuta²⁴,Murakami Teruaki²⁴,Morita Takayoshi²⁴,Kato Yasuhiro²⁴,Hirata Haruhiko²,Takeda Yoshito²,Okuzaki Daisuke⁵⁶⁷⁸^ORCID,Sakaguchi Shimon⁹¹⁰,Kumanogoh Atsushi²⁴⁷⁸,Okada Yukinori³⁷⁸¹¹⁷,Wing James Badger¹¹²^ORCID

Affiliation:

1. Human Immunology Team, Center for Infectious Disease Education and Research, Osaka University, Suita 565-0871, Japan

2. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan

3. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan

4. Department of Immunopathology, World Premier International Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita 565-0871, Japan

5. Laboratory of Human Immunology (Single Cell Genomics), WPI-IFReC, Osaka University, Suita 565-0871, Japan

6. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan

7. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita 565-0871, Japan

8. CiDER, Osaka University, Suita 565-0871, Japan

9. Laboratory of Experimental Immunology, WPI-IFReC, Osaka University, Suita 565-0871, Japan

10. Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

11. Laboratory of Statistical Immunology, WPI-IFReC, Osaka University, Suita 565-0871, Japan

12. Laboratory of Human Single Cell Immunology, WPI-IFReC, Osaka University, Suita 565-0871, Japan

Abstract

Sex-biased humoral immune responses to COVID-19 patients have been observed, but the cellular basis for this is not understood. Using single-cell proteomics by mass cytometry, we find disrupted regulation of humoral immunity in COVID-19 patients, with a sex-biased loss of circulating follicular regulatory T cells (cTfr) at a significantly greater rate in male patients. In addition, a male sex-associated cellular network of T-peripheral helper, plasma blasts, proliferating and extrafollicular/atypical CD11c + memory B cells was strongly positively correlated with neutralizing antibody concentrations and negatively correlated with cTfr frequency. These results suggest that sex-specific differences to the balance of cTfr and a network of extrafollicular antibody production-associated cell types may be a key factor in the altered humoral immune responses between male and female COVID-19 patients.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2217902120

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