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

Chae Rim Lee¹Seon-Yeong Lee¹Jeonghyeon Moon²Jae-Deog Kim¹Su Been Jeon¹Kun Hee Lee¹Tae Ho Kim¹JeongWon Choi¹Sang-Uk Seo¹Mi-La Cho^3*

• ¹the catholic university of korea, College of Medicine, seocho-gu, Republic of korea, Seoul, Republic of Korea
• ²Yale School of Medicine, New Haven, United States
• ³Catholic University of Korea, Seoul, Republic of Korea

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. 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). 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 vimenitn immunized mice were also significantly increased. 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.