Establishment of a mouse model of Sjögren syndrome-related interstitial lung disease

Abstract

Sjögren syndrome-related interstitial lung disease (SS-ILD) is a severe complication associated with significant morbidity and mortality. Despite its clinical importance, the underlying pathogenesis remains poorly understood, and effective therapeutic strategies are limited. The development of a reliable animal model for SS-ILD is crucial for elucidating disease mechanisms and facilitating the discovery of novel treatments. In this study, we established a SS-ILD mouse model by administering 3 mg/kg bleomycin (BLM) via tracheal exposure to NOD/Ltj mice, a spontaneous model of Sjögren syndrome, with ICR mice serving as controls. The successful induction of Sjögren syndrome was confirmed through histopathology, and SSA/SSB ELISAs. Following BLM administration, lung inflammation and fibrosis were evaluated in ICR and NOD/Ltj mice by imaging, histopathology, and flow cytometry. Both ICR and NOD/Ltj mice developed lung inflammation and fibrosis after BLM exposure. However, NOD/Ltj mice exhibited a more pronounced immune response in the lung, characterized by increased infiltration of immune cells, including monocytes, monocyte-derived macrophages, dendritic cells, neutrophils, T cells, and B cells. This model successfully recapitulates key features of SS-ILD, including concurrent lymphocyte infiltration in the salivary glands and inflammation and fibrosis in the lungs. This study established a novel SS-ILD mouse model replicating human disease pathology, offering a valuable tool for investigating pathogenesis and advancing therapeutic development.

Keywords: NOD/Ltj; Sjögren’s syndrome; bleomycin; interstitial lung disease; mouse model.