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-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 for patients with lung fibrosis.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of interest statement: All other authors declare they have no competing interests.
We added new data regarding the role of IL-18 to mediate the anti fibrotic effect of the PAM of P2RX7. We removed data on human since the result are not statistically significant