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

Morgane Gossez, Clara Vigneron, Alexandra Vandermoeten, Margot Lepage, Louise Courcol, Remy Coudereau, Helena Paidassai, Laurent Jallades, Jonathan Lopez, Khalil Kandara, Marine Ortillon, Marine Mommert, Astrid Fabri, Estelle Peronnet, Clémence Grosjean, Marielle Buisson, Anne-Claire Lukaszewicz, Thomas Rimmelé, Laurent Argaud, Martin Cour, Bénédicte F. Py, Olivier Thaunat, Thierry Defrance, Guillaume Monneret and Fabienne Venet ()
Additional contact information
Morgane Gossez: Lyon-Sud & Edouard Herriot University Hospitals
Clara Vigneron: ENS de Lyon
Alexandra Vandermoeten: Structure Fédérative de Recherche (SFR) Santé Lyon Est
Margot Lepage: Lyon-Sud & Edouard Herriot University Hospitals
Louise Courcol: ENS de Lyon
Remy Coudereau: Lyon-Sud & Edouard Herriot University Hospitals
Helena Paidassai: ENS de Lyon
Laurent Jallades: ENS de Lyon
Jonathan Lopez: Lyon Sud University Hospital
Khalil Kandara: Lyon-Sud & Edouard Herriot University Hospitals
Marine Ortillon: Lyon-Sud & Edouard Herriot University Hospitals
Marine Mommert: bioMérieux)
Astrid Fabri: Lyon-Sud & Edouard Herriot University Hospitals
Estelle Peronnet: bioMérieux)
Clémence Grosjean: bioMérieux)
Marielle Buisson: Hospices Civils de Lyon
Anne-Claire Lukaszewicz: bioMérieux)
Thomas Rimmelé: bioMérieux)
Laurent Argaud: Edouard Herriot Hospital
Martin Cour: Edouard Herriot Hospital
Bénédicte F. Py: ENS de Lyon
Olivier Thaunat: ENS de Lyon
Thierry Defrance: ENS de Lyon
Guillaume Monneret: Lyon-Sud & Edouard Herriot University Hospitals
Fabienne Venet: Lyon-Sud & Edouard Herriot University Hospitals

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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+CD44+B220LowCD138+IgM+ 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.

Date: 2025
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DOI: 10.1038/s41467-025-57706-9

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