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bioRxiv · 10.1101/2022.12.15.520590

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

Janho dit Hreich, S.·Juhel, T.·Leroy, S.·Brau, F.·hofman, v.·hofman, p.·Vouret-Craviari, V.
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Abstract

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-{gamma} production by lung T cells leading to a decreased production of IL-17 and TGF{beta}. 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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Janho dit Hreich, S., Juhel, T., Leroy, S., Brau, F., hofman, v., hofman, p., Vouret-Craviari, V.. 2022-12-18. Activation of the P2RX7/IL-18 pathway in immune cells inhibits lung fibrosis. https://doi.org/10.1101/2022.12.15.520590

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