FXR/Sptlc2 signaling in severe lung injury helps lung immune cells clear damaged mitochondria and reduce inflammation

Activation of the nuclear receptor Nr1h4 (FXR) enhances mitophagy in alveolar macrophages.

• Mitophagy is crucial for maintaining mitochondrial health in alveolar macrophages during lung inflammation.
• FXR acts as a transcriptional regulator that increases mitophagy by upregulating a specific protein, Sptlc2.
• Enhanced mitophagy promotes an anti-inflammatory macrophage phenotype, reducing oxidative stress and inflammatory markers.
• Deficiency in FXR leads to impaired mitophagy, worsening pulmonary inflammation and lung injury in animal models.
• The findings suggest that targeting the FXR/Sptlc2 pathway may offer new therapeutic strategies for acute respiratory distress syndrome.

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