Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/54647

Título:

PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

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Autor:

Duhalde Vega, Maite
Olivera, Daniela
Davanzo, Gustavo Gastão
Bertullo, Mauricio
Noya, Verónica
Fabiano de Souza, Gabriela
Primon Muraro, Stéfanie
Castro, Ícaro
Arévalo, Ana Paula
Crispo, Martina
Galliussi, Germán
Russo, Sofía
Charbonnier, David
Rammauro, Florencia
Jeldres, Mathías
Alamón, Catalina
Varela, Valentina
Batthyany, Carlos
Bollati-Fogolín, Mariela
Oppezzo, Pablo
Pritsch, Otto
Proença-Módena, José Luiz
Nakaya, Helder I.
Trías, Emiliano
Barbeito, Luis
Anegon, Ignacio
Cuturi, María Cristina
Moraes-Vieira, Pedro
Segovia, Mercedes
Hill, Marcelo

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COVID-19
LINFOCITOS T
INMUNIDAD
SARS-CoV-2
HUMANOS
RECONOCIMIENTO DE INMUNIDAD INNATA
VIRUS DE LA HEPATITIS MURINA
PROTEÍNAS DE PUNTO DE CONTROL INMUNITARIO
INHIBIDORES DE PUNTOS DE CONTROL INMUNOLÓGICO
PROTEÍNA 2 LIGANDO DE MUERTE CELULAR PROGRAMADA 1

Año de publicación:

2022

Contenido:

Resumen:

Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2–related murine β-coronavirus. Tmem176b−/− mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.

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American Association for the Advancement of Science

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Science Advances. 2022;8(38)

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Citación:

Duhalde Vega M, Olivera D, Davanzo G y Bertullo M. PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease. Science Advances [en línea]. 2022;8(38). 13 p.

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Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)

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