Unraveling the Interactive Role of Mitochondrial Dysfunction in Promoting Macrophage Polarization in Pulmonary
Jiajia Zou1,2, Junling Jian2, Dehua Ge1
1School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Abstract:
Pulmonary fibrosis (PF) is a chronic, irreversible interstitial lung disease. There is no effective treatment or drug that can completely cure this disease. The pathogenesis is still unclear. In recent years, several scholars have reported that the main cause of PF is an imbalance in the inflammatory response and abnormal repair after lung injury. Lung macrophages, as immune cells in vivo, play an important role in regulating the immune response and immune tolerance and promoting lung injury repair through polarization. Recent studies have highlighted the importance of mitochondria in lung fibrosis, safeguarding cellular homeostasis and metabolic roles, and their ability to influence the progression of lung fibrosis by mediating macrophage polarization within lung cells. However, the regulation of macrophage polarization by impaired mitochondrial function remains largely unknown. In this review, we intend to summarize the associations of mitochondrial dysfunction, including mitochondrial dynamics, increased ROS production, mitochondrial DNA (mtDNA) leakage, and inflammatory vesicle activation, with the key mechanisms driving the polarization of both M1-type and M2-type macrophages, as well as further explore the role of mitochondria as key control centers for macrophage polarization, which may lead to novel therapeutic approaches to target and/or reverse disease progression.
Insights
Mitochondrial dysfunction, including increased ROS and inflammation, drives macrophage polarization, worsening pulmonary fibrosis (PF). Targeting mitochondria may offer new treatments for this irreversible lung disease.
Area of Science:
- Pulmonary medicine
- Immunology
- Cell biology
Background:
- Pulmonary fibrosis (PF) is a chronic, irreversible lung disease with unclear pathogenesis.
- Macrophage polarization is crucial for lung injury repair but can contribute to PF.
- Mitochondria play a role in cellular homeostasis and influence PF progression via macrophage polarization.
Purpose of the Study:
- To review the association between mitochondrial dysfunction and macrophage polarization in PF.
- To explore how mitochondrial dynamics, ROS, mtDNA leakage, and inflammasome activation impact M1/M2 macrophage polarization.
- To highlight mitochondria's role in controlling macrophage polarization for potential therapeutic strategies.
Main Methods:
- Literature review summarizing current research on mitochondrial dysfunction and macrophage polarization in PF.
- Analysis of mechanisms linking mitochondrial impairments (dynamics, ROS, mtDNA, inflammasomes) to macrophage polarization.
- Exploration of mitochondria as central regulators of macrophage phenotypes in lung fibrosis.
Main Results:
- Mitochondrial dysfunction, characterized by altered dynamics, elevated ROS, mtDNA release, and inflammasome activation, is linked to aberrant macrophage polarization.
- These mitochondrial defects promote pro-inflammatory M1 and impair anti-inflammatory M2 macrophage phenotypes, exacerbating PF.
- Mitochondria are identified as key regulators of macrophage polarization in the context of lung fibrosis.
Conclusions:
- Impaired mitochondrial function significantly contributes to the pathogenesis of pulmonary fibrosis by skewing macrophage polarization.
- Understanding these mitochondrial-macrophage interactions offers potential therapeutic targets for reversing or halting PF progression.
- Targeting mitochondrial pathways may provide novel strategies for treating pulmonary fibrosis.
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