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Siglec-F Protects Against Elastase-induced Lung Inflammation and Emphysema in Mice

ABSTRACT: Airspace macrophages (AMs) are essential for maintaining lung homeostasis. Their activity must be tightly controlled to prevent excessive immune responses and tissue damage, such as emphysematous alveolar destruction. Siglec-F is a canonical marker of AMs, but its functional role in lung disease remains unclear. Here, we investigated the role of Siglec-F in a murine model of elastase-induced emphysema. We found that Siglec-F-deficient mice exhibited worsened emphysematous phenotypes, along with accumulation and transcriptional reprogramming of resident AMs (RAMs). Transcriptomic profiling of Siglec-F-deficient RAMs revealed dysregulation of key pathways involved in tissue repair, including extracellular matrix degradation, TGF-β signaling, and phagocytosis. These findings demonstrate that Siglec-F is critical for restraining RAM activity and preserving alveolar integrity during injury. Our study provides new insight into the immunoregulatory function of Siglec-F in a tissue-destructive context and highlights the potential protective roles of Siglec signaling in chronic lung disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE307353 | GEO | 2026/02/24

REPOSITORIES: GEO

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