Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis

Janho Dit Hreich, Serena; Juhel, Thierry; Leroy, Sylvie; Ghinet, Alina; Brau, Frederic; Hofman, Véronique; Hofman, Paul; Vouret-Craviari, Valérie

Type de document :

Article dans une revue scientifique: Article original

Titre :

Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis

Auteur(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]

Titre de la revue :

Elife

Éditeur :

eLife Sciences Publication

Date de publication :

2023-12-04

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Chimie

Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL

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