The role of macrophage polarization and cellular crosstalk in the pulmonary fibrotic microenvironment: a review

Abstract

Pulmonary fibrosis (PF) is a progressive interstitial inflammatory disease with a high mortality rate. Patients with PF commonly experience a chronic dry cough and progressive dyspnoea for years without effective mitigation. The pathogenesis of PF is believed to be associated with dysfunctional macrophage polarization, fibroblast proliferation, and the loss of epithelial cells. Thus, it is of great importance and necessity to explore the interactions among macrophages, fibroblasts, and alveolar epithelial cells in lung fibrosis, as well as in the pro-fibrotic microenvironment. In this review, we discuss the latest studies that have investigated macrophage polarization and activation of non-immune cells in the context of PF pathogenesis and progression. Next, we discuss how profibrotic cellular crosstalk is promoted in the PF microenvironment by multiple cytokines, chemokines, and signalling pathways. And finally, we discuss the potential mechanisms of fibrogenesis development and efficient therapeutic strategies for the disease. Herein, we provide a comprehensive summary of the vital role of macrophage polarization in PF and its profibrotic crosstalk with fibroblasts and alveolar epithelial cells and suggest potential treatment strategies to target their cellular communication in the microenvironment.

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

“…Lung B and T cells are well described for COVID-19 [147, 148]; however, iron deficiency is generally associated with impaired B and T cell responses [149, 150]. The Interstitial macrophages are generally anti-inflammatory during disease processes [151] and Ear2 is upregulated on alveolar macrophages under Th2 conditions [152], so reduced abundance scores for these two cell types in iron deficient mice (Fig. 7b) may be associated with the elevated Th1/Th2 ratios (Fig.…”