Work

Vimentin immunization induces TH2/TH17 cell activation and autoantibody production in a novel mouse model of bleomycin induced systemic sclerosis

Year: 2025

Type: article

Abstract: Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and lung tissues. Currently available drugs delay SSc progression but do not reverse the sclerotic lesions or cure the disease. Studies of its pathogenesis have been hindered by the lack of an appropriate animal model, as the widely used mouse model of bleomycin (BLM)-induced scleroderma does not reproduce the immune cell activation seen in humans. Methods: Here we describe an improved mouse model of SSc, achieved by combining BLM administration with immunization against the structural protein vimentin, injected in homogenized form with complete Freund's adjuvant (CFA). Results: An examination of the immune cell modifications and pathological changes in skin and lung showed both more severe fibrosis and an increase in systemic Th2 and Th17 cells and autoantibodies compared to mice treated with BLM alone. The levels of pro-inflammatory cytokines in the lesions of vimentin-immunized mice were also significantly increased. Discussion: This improved model system offers dual advantages for advancing SSc research: it enables deeper mechanistic investigation of the interconnected pathways driving both fibrosis and autoimmune activation, while simultaneously providing a more relevant preclinical platform for evaluating novel therapeutic strategies targeting multiple disease components.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1639601