DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand–receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

DNA折纸能够在空间上将分子组织成具有纳米精度的复杂几何图案。在这里，我们描述了一种可重构的二维 DNA 折纸，其具有几何图案的 CD95 配体，可调节免疫细胞信号传导以减轻类风湿性关节炎。为了响应 pH 值变化，该装置从封闭结构可逆地转变为开放结构，显示出分子间距约为 10 nm 的 CD95 配体的六边形图案，精确地反映了免疫细胞表面 CD95 受体簇的空间排列。在胶原诱导的关节炎小鼠模型中，DNA 折纸在位于发炎滑膜组织中的激活免疫细胞中引发 CD95 死亡诱导信号的强烈和选择性激活。这种局部免疫耐受可以改善关节损伤，且没有明显的副作用。该装置可以对细胞信号传导进行精确的空间控制，扩大我们对配体-受体相互作用的理解，并且是开发针对这些相互作用的药理干预措施的有前途的平台。