徐再靜曾博修HSU, TSAI-CHINGTZANG, BOR-SHOW林聖軒LIN, SHENG-HSUANSHENG-HSUANLIN醫學研究所碩士班2026-10-292030-07-3120252025-07-21https://handle.ncl.edu.tw/11296/5knvj9https://scholars.csmu.edu.tw/handle/123456789/36749外泌體 (Exosome, Exo) 是一種由細胞所分泌的微小囊泡，它們攜帶各種分子，如蛋白質、脂質和核酸，並且透過這些分子來影響其他細胞，也在疾病機轉中扮演著重要的角色。文獻回顧已知人類微小病毒B19 (Human Parvovirus B19, B19V) 感染可能引發或加劇自體免疫疾病，如紅斑性狼瘡和系統性硬化症等。活化的巨噬細胞已知通常可分為M1和M2兩類，其中M1巨噬細胞極化和許多發炎疾病機轉有關，例如自體免疫疾病。先前實驗室研究發現，B19V VP1u重組蛋白可以活化巨噬細胞及促進發炎細胞激素的分泌，如TNFα, IL-6和IL-1β。最近更發現B19V VP1u會加劇系統性硬化症小鼠模型的皮膚纖維化。然而B19V VP1u是否透過活化巨噬細胞所分泌的外泌體來惡化疾病的發展，目前仍不清楚。因此本論文將進一步利用細胞和動物實驗來進行B19V所誘發之巨噬細胞外泌體的作用探討。研究結果顯示，B19V VP1u誘發巨噬細胞所分泌的外泌體 (B19V VP1u Exo)，不僅可以促進M1巨噬細胞的極化，並且相較於M0巨噬細胞所分泌的外泌體 (Control Exo)，B19V VP1u Exo會加劇系統性硬化症小鼠模型真皮纖維化的情形。綜合以上結果發現，B19V感染所誘發細胞分泌的外泌體可以透過調控M1巨噬細胞發炎反應來影響皮膚纖維化的進展。Exosomes (Exo) are small vesicles secreted by cells that carry various molecules, such as proteins, lipids, and nucleic acids. Exosomes influence other cells through these molecules and play essential roles in disease mechanisms. Studies have demonstrated that human parvovirus B19 (B19V) infection may trigger or exacerbate autoimmune diseases, including lupus erythematosus and systemic sclerosis (SSc). Activated macrophages are generally categorized into M1 and M2 subtypes, with M1 macrophage polarization being closely associated with the pathogenesis of various inflammatory diseases, like autoimmune disorders. Our previous studies showed that the recombinant B19V-VP1u protein can activate macrophages and promote the secretion of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β. Recently, we found that the B19V-VP1u recombinant protein may exacerbate dermal fibrosis in a mouse model for SSc. However, whether B19V-VP1u exacerbates disease progression through exosomes secreted by activated macrophages remains unclear. Therefore, this study aims to investigate the function of macrophage-derived exosomes induced by B19V-VP1u through cellular and animal experiments. The results showed that exosomes secreted by B19V-VP1u-activated macrophages (B19V-VP1u Exo) not only promote M1 macrophage polarization but also exacerbate dermal fibrosis in the SSc mouse model, when compared to exosomes secreted by non-activated macrophages (Control Exo). In conclusion, these findings indicate that exosomes secreted by cells induced by B19V infection can affect the progression of skin fibrosis by regulating the inflammatory response of M1 macrophages.外泌體人類微小病毒B19巨噬細胞系統性硬化症exosomeshuman parvovirus B19macrophagessystemic sclerosisthesis