Study Identifies iRhom2 as Key Driver of Acute Lung Inflammation, Potential Drug Target
Researchers found that the protein iRhom2 plays a critical role in promoting acute lung inflammation by enabling ADAM17 to shed inflammatory molecules. In mouse models of LPS-induced lung inflammation, iRhom2-deficient mice showed significantly reduced neutrophil recruitment and lower levels of inflammatory mediators. The findings suggest that targeting iRhom2 could offer a selective anti-inflammatory therapy with fewer side effects than broader ADAM17 inhibition.
A new study published on bioRxiv demonstrates that iRhom2, a pseudoproteinase predominantly expressed in immune cells and upregulated during inflammation, critically promotes acute lung inflammation through its role as an adapter for ADAM17. Using multiple experimental approaches in mice, researchers showed that iRhom2 knockout mice exhibited reduced neutrophil recruitment into lung airways and decreased shedding of inflammatory molecules including TNF-α and IL-6R compared to normal mice. The study found that iRhom2 functions in both immune cells and resident lung tissue cells to initiate inflammatory responses. Notably, the researchers observed that impaired shedding of L-selectin in iRhom2-deficient mice correlated with decreased neutrophil recruitment, suggesting a mechanistic link. The findings indicate that selectively targeting iRhom2 could suppress ADAM17-mediated inflammation while preserving basal ADAM17 activity through the related protein iRhom1, potentially offering a more targeted therapeutic approach with reduced side effects.
Limitations & open questions
The article does not discuss the current state of clinical translation or whether any iRhom2-targeting compounds are in development. Additionally, it lacks discussion of how findings in mouse models might translate to human lung inflammation or whether iRhom2 plays similar roles in other inflammatory conditions beyond acute lung inflammation.
What different sources said
- bioRxivCenter
The pseudoproteinase iRhom2 critically promotes acute lung inflammation
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