Targeting defective Toll-like receptor-3 function and idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a disease of the lung parenchyma that is invariably fatal with a median survival of 2 - 3 years. Despite considerable progress in defining the natural history of the disease, many features of IPF pathogenesis remain poorly understood. Several recent studies have highlighted links between pattern recognition receptors of innate immunity termed 'Toll-like receptors' (TLRs) and the aberrant fibrogenesis that characterizes IPF. Areas covered: In this paper, we discuss the natural history of IPF and the identification of several distinct clinical phenotypes in recent years. TLRs are receptors that recognize pathogen-and/or danger-associated molecular patterns and promote an appropriate immune response. We describe in detail some of the recent works linking defective TLR3 function and an aggressive phenotype in IPF and explore the mechanisms and potential clinical implications of this initial observation. Expert opinion: We explore the potential role of TLRs in this setting. We discuss recent genetic studies and the implications for future research. We propose a model of dysregulated innate immune recognition and aberrant lung healing. The potential role of research in aiding the design of clinical trials and the evidence for targeting defective TLR3 function in IPF is presented.