Emerging roles of basophils in the resolution of acute respiratory distress syndrome.

Summary

Using an LPS-induced mouse model with genetic tools and single-cell transcriptomics, the authors show that basophils are essential for resolving ARDS-like lung inflammation. Basophil-derived IL-4 signals to neutrophils to suppress survival and pro-inflammatory programs, enabling resolution.

Key Findings

• Basophil depletion impaired the resolution, but not induction, of LPS-induced lung inflammation in mice.
• Basophils in the lung were the main source of IL-4; basophil-specific IL-4 deficiency prevented inflammation resolution.
• Neutrophil-specific IL-4 receptor deficiency also blocked resolution, indicating IL-4 signaling to neutrophils is required.
• Single-cell transcriptomics showed IL-4 suppressed neutrophil anti-apoptotic and pro-inflammatory gene expression.

Clinical Implications

Targeting the IL-4 signaling axis or basophil function could become a pro-resolution therapeutic strategy in ARDS. Peripheral basophil counts might also serve as a prognostic biomarker to stratify patients.

Limitations

• Findings are from a mouse LPS model and may not fully translate to human ARDS.
• Therapeutic modulation of the IL-4 axis was not tested in interventional experiments.

Future Directions

Validate basophil–IL-4–neutrophil interactions in human ARDS samples, and test IL-4 or basophil-targeted pro-resolution interventions in preclinical models and early-phase trials.