Vivian Ma Yu-Heng, Sparkes Amanda, Saha Shrayasee, Gariépy Jean
Physical Sciences, Sunnybrook Research Institute, 2075 Bayview Ave., Room M7-436, Toronto, ON M4N 3M5, Canada.
Department of Pharmaceutical Sciences, University of Toronto, 2075 Bayview Ave., Room M7-434, Toronto, ON M4N 3M5, Canada.
Cell Immunol. 2022 Sep;379:104581. doi: 10.1016/j.cellimm.2022.104581. Epub 2022 Jul 29.
VISTA has been proposed to function both as a ligand and a receptor to dampen immune responses, although the role of VISTA as a ligand on myeloid cells has been largely ignored. We observed that a VISTA receptor is rapidly expressed on the surface of macrophages and neutrophils upon exposure to lipopolysaccharides (LPS). Importantly, treating LPS-stimulated macrophages and neutrophils ex vivo with a high-avidity agonist of the VISTA receptor (VISTA.COMP) results in the downregulation of pro-inflammatory cytokines and the increased expression of immunoregulatory genes. Finally, the in vivo administration of VISTA.COMP attenuated the rise in circulating TNFα, IL-6, and IL-12p40 in LPS-treated mice.
有人提出VISTA既能作为配体又能作为受体来抑制免疫反应，尽管VISTA作为髓系细胞上配体的作用在很大程度上被忽视了。我们观察到，巨噬细胞和中性粒细胞在暴露于脂多糖（LPS）后，其表面会迅速表达VISTA受体。重要的是，用VISTA受体的高亲和力激动剂（VISTA.COMP）在体外处理LPS刺激的巨噬细胞和中性粒细胞，会导致促炎细胞因子的下调和免疫调节基因表达的增加。最后，在体内给予VISTA.COMP可减轻LPS处理小鼠循环中TNFα、IL-6和IL-12p40的升高。
