Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease with significant unmet need, and only a few therapeutic options slow decline rather than improve function. An expanding fibrotic niche is one hallmark of this disease, comprising a multicellular environment characterized by epithelial dysfunction and death, infiltration of peripheral immune cells, differentiation of fibroblasts and immune cells, extracellular matrix turnover and deposition of fibrillar collagen. Inflammation is a master regulator spanning all aspects of this fibrotic niche through cellular players and signaling mediators that can be split into three primary types. In many immune responses, the inflammatory milieu is dominated by one type of inflammation at a time, but recent findings suggest there might be more spatial and kinetic overlap present in fibrotic diseases, including IPF, than previously appreciated. In this Review, we summarize some of the key cellular players and soluble mediators involved in IPF progression and how distinct types of inflammation jointly regulate disease progression in concert rather than focus on individual cytokines or immune cells.