Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue eLife Année : 2023

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

Serena Janho Dit Hreich
Thierry Juhel
  • Fonction : Auteur
Sylvie Leroy
  • Fonction : Auteur
Frederic Brau
Véronique Hofman
  • Fonction : Auteur
Paul Hofman
  • Fonction : Auteur
Valérie Vouret-Craviari

Résumé

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.
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Dates et versions

hal-04403482 , version 1 (18-01-2024)

Identifiants

  • HAL Id : hal-04403482 , version 1

Citer

Serena Janho Dit Hreich, Thierry Juhel, Sylvie Leroy, Alina Ghinet, Frederic Brau, et al.. Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis. eLife, 2023, 12. ⟨hal-04403482⟩
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