Nature Communications

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

M Morgane Gossez C Clara Vigneron A Alexandra Vandermoeten M Margot Lepage L Louise Courcol R Remy Coudereau H Helena Paidassai L Laurent Jallades J Jonathan Lopez K Khalil Kandara M Marine Ortillon M Marine Mommert A Astrid Fabri E Estelle Peronnet C Clémence Grosjean M Marielle Buisson L Laurent Argaud M Martin Cour S Sophie Arnal C Caroline Augris-Mathieu F Frédérique Bayle L Liana Caruso C Charles-Eric Ber A Asma Ben-Amor A Anne-Sophie Bellocq F Farida Benatir A Anne Bertin-Maghit M Marc Bertin-Maghit A André Boibieux Y Yves Bouffard J Jean-Christophe Cejka V Valérie Cerro J Jullien Crozon-Clauzel J Julien Davidson S Sophie Debord-Peguet B Benjamin Delwarde R Robert Deleat-Besson C Claire Delsuc B Bertrand Devigne L Laure Fayolle-Pivot A Alexandre Faure B Bernard Floccard J Julie Gatel C Charline Genin T Thibaut Girardot A Arnaud Gregoire B Baptiste Hengy L Laetitia Huriaux C Catherine Jadaud A Alain Lepape V Véronique Leray A Anne-Claire Lukaszewicz G Guillaume Marcotte O Olivier Martin M Marie Matray D Delphine Maucort-Boulch P Pascal Meuret C Céline Monard F Florent Moriceau N Nathalie Panel N Najia Rahali T Thomas Rimmelé C Cyrille Truc T Thomas Uberti H Hélène Vallin S Sylvie Tissot A Abbès Zadam S Sophie Blein K Karen Brengel-Pesce E Elisabeth Cerrato V Valérie Cheynet E Emmanuelle Gallet-Gorius A Audrey Guichard C Camille Jourdan N Natacha Koenig F François Mallet B Boris Meunier V Virginie Moucadel G Guy Oriol A Alexandre Pachot C Claire Schrevel O Olivier Tabone J Julien Textoris J Javier Yugueros Marcos J Jérémie Becker F Frédéric Bequet Y Yacine Bounab F Florian Brajon B Bertrand Canard M Muriel Collus N Nathalie Garcon I Irène Gorse C Cyril Guyard F Fabien Lavocat P Philippe Leissner K Karen Louis M Maxime Mistretta J Jeanne Moriniere Y Yoann Mouscaz L Laura Noailles F Frédéric Reynier C Cindy Riffaud M Mary-Luz Rol N Nicolas Sapay T Trang Tran C Christophe Vedrine C Christophe Carre P Pierre Cortez A Aymeric De Monfort K Karine Florin L Laurent Fraisse I Isabelle Fugier S Sandrine Payrard A Annick Peleraux L Laurence Quemeneur A Andrew Griffiths S Stephanie Toetsch T Teri Ashton P Peter J. Gough S Scott B. Berger D David Gardiner I Iain Gillespie A Aidan Macnamara A Aparna Raychaudhuri R Rob Smylie L Lionel Tan C Craig Tipple R Remi Pescarmona L Lorna Garnier C Christine Lombard M Magali Perret M Marine Villard F Filippo Conti M Marie Groussaud L Laetitia Itah I Inesse Boussaha F Françoise Poitevin-Later C Christophe Malcus E Eleonore Micoud F Florent Wallet M Marie-Charlotte Delignette F Frederic Dailler M Marie Simon A Auguste Dargent P Pierre-Jean Bertrand N Neven Stevic M Marion Provent L Laurie Bignet J Jean-Christophe Richard L Laurent Bitker M Mehdi Mezidi L Loredana Baboi B Bénédicte F. Py O Olivier Thaunat (Centre International de Recherche en Immunologie, Université de Lyon, INSERM U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon) T Thierry Defrance G Guillaume Monneret F Fabienne Venet

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.

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Article Details

Volume / Issue Vol. 16, Issue 1
Published March 28, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (157)

M

Morgane Gossez

C

Clara Vigneron

A

Alexandra Vandermoeten

M

Margot Lepage

L

Louise Courcol

R

Remy Coudereau

H

Helena Paidassai

L

Laurent Jallades

J

Jonathan Lopez

K

Khalil Kandara

M

Marine Ortillon

M

Marine Mommert

A

Astrid Fabri

E

Estelle Peronnet

C

Clémence Grosjean

M

Marielle Buisson

L

Laurent Argaud

M

Martin Cour

S

Sophie Arnal

C

Caroline Augris-Mathieu

F

Frédérique Bayle

L

Liana Caruso

C

Charles-Eric Ber

A

Asma Ben-Amor

A

Anne-Sophie Bellocq

F

Farida Benatir

A

Anne Bertin-Maghit

M

Marc Bertin-Maghit

A

André Boibieux

Y

Yves Bouffard

J

Jean-Christophe Cejka

V

Valérie Cerro

J

Jullien Crozon-Clauzel

J

Julien Davidson

S

Sophie Debord-Peguet

B

Benjamin Delwarde

R

Robert Deleat-Besson

C

Claire Delsuc

B

Bertrand Devigne

L

Laure Fayolle-Pivot

A

Alexandre Faure

B

Bernard Floccard

J

Julie Gatel

C

Charline Genin

T

Thibaut Girardot

A

Arnaud Gregoire

B

Baptiste Hengy

L

Laetitia Huriaux

C

Catherine Jadaud

A

Alain Lepape

V

Véronique Leray

A

Anne-Claire Lukaszewicz

G

Guillaume Marcotte

O

Olivier Martin

M

Marie Matray

D

Delphine Maucort-Boulch

P

Pascal Meuret

C

Céline Monard

F

Florent Moriceau

N

Nathalie Panel

N

Najia Rahali

T

Thomas Rimmelé

C

Cyrille Truc

T

Thomas Uberti

H

Hélène Vallin

S

Sylvie Tissot

A

Abbès Zadam

S

Sophie Blein

K

Karen Brengel-Pesce

E

Elisabeth Cerrato

V

Valérie Cheynet

E

Emmanuelle Gallet-Gorius

A

Audrey Guichard

C

Camille Jourdan

N

Natacha Koenig

F

François Mallet

B

Boris Meunier

V

Virginie Moucadel

G

Guy Oriol

A

Alexandre Pachot

C

Claire Schrevel

O

Olivier Tabone

J

Julien Textoris

J

Javier Yugueros Marcos

J

Jérémie Becker

F

Frédéric Bequet

Y

Yacine Bounab

F

Florian Brajon

B

Bertrand Canard

M

Muriel Collus

N

Nathalie Garcon

I

Irène Gorse

C

Cyril Guyard

F

Fabien Lavocat

P

Philippe Leissner

K

Karen Louis

M

Maxime Mistretta

J

Jeanne Moriniere

Y

Yoann Mouscaz

L

Laura Noailles

F

Frédéric Reynier

C

Cindy Riffaud

M

Mary-Luz Rol

N

Nicolas Sapay

T

Trang Tran

C

Christophe Vedrine

C

Christophe Carre

P

Pierre Cortez

A

Aymeric De Monfort

K

Karine Florin

L

Laurent Fraisse

I

Isabelle Fugier

S

Sandrine Payrard

A

Annick Peleraux

L

Laurence Quemeneur

A

Andrew Griffiths

S

Stephanie Toetsch

T

Teri Ashton

P

Peter J. Gough

S

Scott B. Berger

D

David Gardiner

I

Iain Gillespie

A

Aidan Macnamara

A

Aparna Raychaudhuri

R

Rob Smylie

L

Lionel Tan

C

Craig Tipple

R

Remi Pescarmona

L

Lorna Garnier

C

Christine Lombard

M

Magali Perret

M

Marine Villard

F

Filippo Conti

M

Marie Groussaud

L

Laetitia Itah

I

Inesse Boussaha

F

Françoise Poitevin-Later

C

Christophe Malcus

E

Eleonore Micoud

F

Florent Wallet

M

Marie-Charlotte Delignette

F

Frederic Dailler

M

Marie Simon

A

Auguste Dargent

P

Pierre-Jean Bertrand

N

Neven Stevic

M

Marion Provent

L

Laurie Bignet

J

Jean-Christophe Richard

L

Laurent Bitker

M

Mehdi Mezidi

L

Loredana Baboi

B

Bénédicte F. Py

O

Olivier Thaunat

Centre International de Recherche en Immunologie, Université de Lyon, INSERM U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon

T

Thierry Defrance

G

Guillaume Monneret

F

Fabienne Venet

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