Autophagy, our cellular clean-up crew, plays a key role in maintaining cellular health by removing damaged components and fighting infections. It also has a profound impact on inflammation.
Here’s how:
Regulating Inflammation: Autophagy helps keep inflammation in check by degrading pro-inflammatory signals, preventing runaway inflammation.
Combatting Infections: It acts as an antimicrobial defense, clearing out pathogens and mitigating inflammatory responses tied to infections.
Balancing Act: When working correctly, autophagy and inflammation are in harmony. However, impaired autophagy can lead to excessive inflammation and tissue damage.
Type I Interferon Interaction: Autophagy interacts with type I IFN pathways, crucial for antiviral responses. It prevents excessive IFN production that could otherwise drive inflammatory pathology.
Immunometabolism: Autophagy affects the metabolic states of immune cells like macrophages and T cells, shaping their responses to inflammation.
Targeted Degradation: Specific receptors in autophagy tag and transport inflammatory cargo for degradation, thus reducing inflammation.
Cell Death Regulation: Autophagy helps counteract inflammatory cell death types such as pyroptosis and necroptosis, linked to various inflammatory diseases.
Lysosomal Fusion: It ensures the fusion of autophagosomes with lysosomes, which is crucial for degrading inflammatory signals and maintaining cellular homeostasis.
When autophagy fails, it can lead to excessive inflammation, contributing to diseases like autoimmunity, cancer, and neurodegeneration. Understanding and modulating this relationship is key to developing therapies for inflammatory diseases.
Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity. 2021;54(3):437-53.
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