Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and the normal tissue environment. Three broad pathways control polarization: epigenetic and cell survival pathways that prolong or shorten macrophage development and viability, the tissue microenvironment, and extrinsic factors, such as microbial products and cytokines released in inflammation. A plethora of advances have provided a framework for rationally purifying, describing, and manipulating macrophage polarization. Here, I assess the current state of knowledge about macrophage polarization and enumerate the major questions about how activated macrophages regulate the physiology of normal and damaged tissues.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive lung scarring and the histological picture of usual interstitial pneumonia (UIP). It is associated with increasing cough and dyspnoea and impaired quality of life. IPF affects ∼3 million people worldwide, with incidence increasing dramatically with age. The diagnostic approach includes the exclusion of other interstitial lung diseases or overlapping conditions and depends on the identification of the UIP pattern, usually with high-resolution CT; lung biopsy might be required in some patients. The UIP pattern is predominantly bilateral, peripheral and with a basal distribution of reticular changes associated with traction bronchiectasis and clusters of subpleural cystic airspaces. The biological processes underlying IPF are thought to reflect an aberrant reparative response to repetitive alveolar epithelial injury in a genetically susceptible ageing individual, although many questions remain on how to define susceptibility. Substantial progress has been made in the understanding of the clinical management of IPF, with the availability of two pharmacotherapeutic agents, pirfenidone and nintedanib, that decrease physiological progression and likely improve progression-free survival. Current efforts are directed at identifying IPF early, potentially relying on combinations of biomarkers that include circulating factors, demographics and imaging data.

Abstract Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune‐regulated and anti‐inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization.