Forde Luke, Gogoi Debananda, Baird Rory, McCarthy Cormac, Keane Michael P, Reeves Emer P, McGrath Emmet E
Pulmonary Clinical Science, Department of Anaesthesia and Critical Care Medicine, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland,
Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland,
J Innate Immun. 2025;17(1):44-55. doi: 10.1159/000543083. Epub 2024 Dec 11.
Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis.
The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate, activate pro-inflammatory responses to innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments.
Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding of pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients.
Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis.
The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate, activate pro-inflammatory responses to innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments.
Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding of pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients.
间质性肺疾病（ILD）是一类了解较少的疾病，其特征为肺实质的弥漫性损伤，并伴有炎症和纤维化。一些间质性肺疾病表现出进行性纤维化表型，致死率高且治疗选择有限，如特发性肺纤维化。
炎症在纤维化进展中所起的作用程度尚不清楚。然而，伤口愈合和纤维化是受多种炎症因子影响的复杂过程。细胞外核苷和核苷酸，包括三磷酸腺苷，可激活对先天免疫的促炎反应，并广泛涉及不同器官的组织纤维化。细胞外核苷酸的促炎作用通过P1和P2嘌呤能受体介导，这些受体在肺和免疫系统中均有表达，并与包括肺纤维化在内的多种肺部疾病有关。本综述整合了关于P1和P2嘌呤能受体信号在肺纤维化中的复杂作用的现有数据，并讨论了新治疗方法的前景。
嘌呤能信号在肺纤维化中发挥着复杂且关键的作用，值得进一步研究。P1和P2受体途径之间复杂的相互作用需要采用综合方法来理解它们的共同影响。虽然临床前模型的证据很有前景，但人体研究对于进一步了解肺纤维化至关重要。受体特异性激动剂和拮抗剂的进展为研究提供了新途径，并可能最终为患者带来新的治疗方法。
间质性肺疾病（ILD）是一类了解较少的疾病，其特征为肺实质的弥漫性损伤，并伴有炎症和纤维化。一些间质性肺疾病表现出进行性纤维化表型，致死率高且治疗选择有限，如特发性肺纤维化。
炎症在纤维化进展中所起的作用程度尚不清楚。然而，伤口愈合和纤维化是受多种炎症因子影响的复杂过程。细胞外核苷和核苷酸，包括三磷酸腺苷，可激活对先天免疫的促炎反应，并广泛涉及不同器官的组织纤维化。细胞外核苷酸的促炎作用通过P1和P2嘌呤能受体介导，这些受体在肺和免疫系统中均有表达，并与包括肺纤维化在内的多种肺部疾病有关。本综述整合了关于P1和P2嘌呤能受体信号在肺纤维化中的复杂作用的现有数据，并讨论了新治疗方法的前景。
嘌呤能信号在肺纤维化中发挥着复杂且关键的作用，值得进一步研究。P1和P2受体途径之间复杂的相互作用需要采用综合方法来理解它们的共同影响。虽然临床前模型的证据很有前景，但人体研究对于进一步了解肺纤维化至关重要。受体特异性激动剂和拮抗剂的进展为研究提供了新途径，并可能最终为患者带来新的治疗方法。
