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Søndergaard, Jonas Nørskov; Tulyeu, Janyerkye; Edahiro, Ryuya; Shirai, Yuya; Yamaguchi, Yuta; Murakami, Teruaki; Morita, Takayoshi; Kato, Yasuhiro; Hirata, Haruhiko; Takeda, Yoshito; Okuzaki, Daisuke; Sakaguchi, Shimon; Kumanogoh, Atsushi; Okada, Yukinori; Wing, James Badger
Proceedings of the National Academy of Sciences - PNAS, 01/2023, Volume: 120, Issue: 4Journal Article
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.
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