SARS-CoV-2 spike protein accelerates systemic sclerosis by increasing inflammatory cytokines, Th17 cells, and fibrosis

• Published in: Journal of inflammation (London, England) England), 2023-12, Vol.20 (1), p.46-46, Article 46
• Main Authors: Jeong, Ha Yeon, Park, Jin-Sil, Woo, Jin Seok, Lee, Kun Hee, Choi, Jeong Won, Kang, Hye Yeon, Na, Hyun Sik, Lee, Yeon Su, Um, In Gyu, Park, Sung-Hwan, Cho, Mi-La
• Format: Article
• Language: English
• Subjects: ACE2; Analysis; Angiotensin-converting enzyme 2; Antiphospholipid antibodies; Autoantibodies; Autoimmune Disease; Autoimmune diseases; Autoimmunity; Bleomycin; Case reports; Coronavirus Disease 2019 (COVID-19); Coronaviruses; COVID-19; Cytokines; Ethylenediaminetetraacetic acid; Fibrosis; Flow cytometry; Health aspects; Helper cells; Immune response; Infections; Inflammation; Laboratory animals; Lung diseases; Lungs; Lymphocytes T; Medical research; Mortality; Phospholipids; Pneumonia; Proteins; Scleroderma (Disease); Severe acute respiratory syndrome coronavirus 2; Skin; Spike protein; Systemic scleroderma; Systemic sclerosis; Thrombosis; Transforming growth factor-b; Transforming growth factors; Western blotting
• ISSN: 1476-9255; 1476-9255
• DOI: 10.1186/s12950-023-00362-x

Coronavirus disease 2019 (COVID-19) induces a dysfunctional immune response, inflammation, autoantibody production, and coagulopathy, which are symptoms that bear resemblance to those of autoimmune diseases, including systemic sclerosis (SSc). While there is a single case report suggesting an association between COVID-19 and SSc, the effects of COVID-19 on SSc are not yet fully understood. Human embryonic kidney 293 (HEK293) cells were transfected with the SARS-CoV-2 spike protein gene, in the presence of TGF-β. The expression levels of fibrosis-related proteins were measured via Western blotting. A bleomycin (BLM)-induced SSc mouse model was employed, wherein mice were injected with the gene encoding the SARS-CoV-2 spike protein and the ACE2 receptor. The levels of fibrosis, autoantibodies, thrombotic factors, and inflammatory cytokines in tissues and serum were analyzed. In vitro, the expression levels of fibrosis marker proteins were elevated in the spike protein group compared to the control group. In vivo, the skin thickness of SSc mice increased following exposure to the SARS-CoV-2 spike protein. Furthermore, the levels of autoantibodies and thrombotic factors, such as anti-phospholipid antibodies (APLA), were significantly increased in the presence of the protein. Flow cytometry analysis revealed increased expression of the proinflammatory cytokine IL-17 in the skin, lungs, and blood. Moreover, tissue fibrosis and levels of inflammatory cytokines in skin and lung tissues were markedly escalated in SSc mice subjected to the protein. COVID-19 may accelerate the development and progression of SSc by intensifying fibrosis through the upregulation of inflammation, autoantibody production, and thrombosis.