The Inflammasome NLR Family Pyrin Domain-Containing Protein 3 (NLRP3) as a Novel Therapeutic Target for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a dramatic disease without cure. The US Food and Drug Administration -approved drugs, pirfenidone and nintedanib, only slow disease progression. The clinical investigation of novel therapeutic approaches for IPF is an unmet clinical need. Nucleotide binding oligomerization domain-like receptor or NOD-like receptors are pattern recognition receptors capable of binding a large variety of stress factors. NLR family pyrin domain-containing protein 3 (NLRP3), once activated, promotes IL-1b, IL-18 production, and innate immune responses. Multiple reports indicate that the inflammasome NLRP3 is overactivated in IPF patients, leading to increased production of class I IL and collagens. Similarly, data from animal models of pulmonary fibrosis confirm the role of NLRP3 in the development of chronic lung injury and pulmonary fibrosis. This report provides a review of the evidence of NLRP3 activation in IPF and of NLRP3 inhibition in different animal models of fibrosis, and highlights the recent advances in direct and indirect NLRP3 inhibitors.

Automated summary

Idiopathic pulmonary fibrosis (IPF) is an incurable disease and current medications can only slow down disease progression, highlighting the importance of exploring novel therapeutic approaches. The overactivation of NLRP3 in IPF patients has been linked to chronic lung injury and fibrosis development.