PD-L1+ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models

Sepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients' risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1<sup>+</sup>CD44<sup>+</sup>B220<sup>Low</sup>CD138<sup>+</sup>IgM<sup>+</sup> regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor. These observations are recapitulated in three cohorts of critically ill patients with bacterial and viral sepsis in association with increased mortality. Our findings thus reveal the function of regulatory plasma cells in the pathophysiology of sepsis-induced immune alterations, and present a potential therapeutic target for improving immune cell function impaired by sepsis.

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Journal
Nature Communications
Published
2025-03-28
DOI
https://doi.org/10.1038/s41467-025-57706-9
Citations
15
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
11.96

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PD-L1+ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models

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PD-L1+ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models

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article en
15 citations

Abstract

Sepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients' risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1<sup>+</sup>CD44<sup>+</sup>B220<sup>Low</sup>CD138<sup>+</sup>IgM<sup>+</sup> regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor. These observations are recapitulated in three cohorts of critically ill patients with bacterial and viral sepsis in association with increased mortality. Our findings thus reveal the function of regulatory plasma cells in the pathophysiology of sepsis-induced immune alterations, and present a potential therapeutic target for improving immune cell function impaired by sepsis.

Nature CommunicationsVol. 16(1)
Université Claude Bernard Lyon 1 (FR), École Normale Supérieure de Lyon (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Sciences et Lettres (FR), Age UK (GB), Sanofi (France) (FR), Hôpital de la Croix-Rousse (FR), Hospices Civils de Lyon (FR), Hôpital Pierre Wertheimer (FR), Hôpital Lyon Sud (FR), bioMérieux (France) (FR), BIOASTER (FR), Centre International de Recherche en Infectiologie (FR), ESPCI Paris (FR)
Sanofi, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut Universitaire de France, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Etablissement Français du Sang, École Normale Supérieure de Lyon
Good health and well-being
Openalex Percentile: Top 1%
Immune Cell Function and Interaction
11.96
DOIOpen Access PDFOpenAlex
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