Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia; Human Health, Nuclear Science & Technology and Landmark Infrastructure (NSTLI), Australian Nuclear Science and Technology Organisation, Sydney, New South Wales, Australia.
J Invest Dermatol. 2020 Dec;140(12):2398-2407.e1. doi: 10.1016/j.jid.2020.03.973. Epub 2020 May 7.
Psoriasis is a chronic inflammatory autoimmune skin condition that affects millions of people worldwide. It is driven by IL-17-producing CD4 and γδ T cells and targeted by current anti-IL-17 or anti-IL-23 mAb therapies. These treatments are expensive, increase the risk of opportunistic infections, and do not specifically target the inflammatory cascade. Other cells, including inflammatory monocytes, have been shown to migrate to psoriatic plaques in both human disease and the imiquimod-induced mouse model and could thus constitute potential alternative therapeutic targets. In the mouse, immune modifying particles (IMPs) specifically target Ly6C inflammatory monocytes migrating to the site of inflammation, sequestering them in the spleen. In this project, we determined whether IMPs could mitigate the development of imiquimod -induced psoriasis in mice. IMP treatment significantly reduced imiquimod-induced psoriasis severity, decreasing dermal infiltration of Ly6C monocytes as well as early-stage monocyte-derived dermal macrophages. This was associated with reduced levels of hallmark cytokines IL-23 and IL-1β as well as associated IL-17-producing γδ T cells. Our work highlights the crucial importance of inflammatory monocytes in the development of this disease as well as a therapeutic potential for IMP in psoriasis.
银屑病是一种慢性炎症性自身免疫性皮肤病，影响着全球数百万人。它由产生 IL-17 的 CD4 和 γδ T 细胞驱动，目前的抗 IL-17 或抗 IL-23 mAb 疗法针对这些细胞。这些治疗方法昂贵，增加了机会性感染的风险，并且不能特异性地针对炎症级联反应。其他细胞，包括炎症性单核细胞，已经在人类疾病和咪喹莫特诱导的小鼠模型中显示出向银屑病斑块迁移的现象，因此可以构成潜在的替代治疗靶点。在小鼠中，免疫修饰颗粒（IMPs）特异性地靶向迁移到炎症部位的 Ly6C 炎症性单核细胞，将它们隔离在脾脏中。在本项目中，我们确定了 IMP 是否可以减轻咪喹莫特诱导的小鼠银屑病的发展。IMPs 治疗显著减轻了咪喹莫特诱导的银屑病的严重程度，减少了真皮中 Ly6C 单核细胞以及早期单核细胞衍生的真皮巨噬细胞的浸润。这与标志性细胞因子 IL-23 和 IL-1β 以及相关的 IL-17 产生的 γδ T 细胞水平降低有关。我们的工作强调了炎症性单核细胞在这种疾病发展中的至关重要性，以及 IMP 在银屑病中的治疗潜力。
