Activation of the P2RX7/IL-18 pathway in ...
Document type :
Article dans une revue scientifique: Article original
Title :
Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis
Author(s) :
Janho Dit Hreich, Serena [Auteur]
Juhel, Thierry [Auteur]
Leroy, Sylvie [Auteur]
Ghinet, Alina [Auteur]
JUNIA [JUNIA]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Brau, Frederic [Auteur]
Hofman, Véronique [Auteur]
Hofman, Paul [Auteur]
Vouret-Craviari, Valérie [Auteur]
Juhel, Thierry [Auteur]
Leroy, Sylvie [Auteur]
Ghinet, Alina [Auteur]
JUNIA [JUNIA]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Brau, Frederic [Auteur]
Hofman, Véronique [Auteur]
Hofman, Paul [Auteur]
Vouret-Craviari, Valérie [Auteur]
Journal title :
Elife
Publisher :
eLife Sciences Publication
Publication date :
2023-12-04
HAL domain(s) :
Sciences du Vivant [q-bio]
Chimie
Chimie
English abstract : [en]
Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated ...
Show more >Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. We show here that the P2RX7/IL-18/IFNG axis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an anti-fibrotic immune environment, with notably an enhanced IL-18-dependent IFN-γ production by lung T cells leading to a decreased production of IL-17 and TGFβ. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy to help patients with lung fibrosis.Show less >
Show more >Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. We show here that the P2RX7/IL-18/IFNG axis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an anti-fibrotic immune environment, with notably an enhanced IL-18-dependent IFN-γ production by lung T cells leading to a decreased production of IL-17 and TGFβ. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy to help patients with lung fibrosis.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Collections :
Source :
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