As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals’ lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon’s lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer and eliminated immune-related colitis triggered by kinase inhibitors and immune checkpoint blockade.

作为一种慢性自身炎症，溃疡性结肠炎通常通过全身免疫抑制剂进行治疗。在这里，我们在三种已建立的溃疡性结肠炎小鼠模型中展示了皮下注射的结肠特异性免疫抑制生态位，该生态位由结肠上皮细胞、脱细胞结肠细胞外基质和纳米纤维组成，并用程序性死亡配体 1 CD86（一种转化生长的肽模拟物）进行功能化因子-β 1 和免疫抑制性小分子来氟米特可诱导肠道免疫耐受并减少动物下胃肠道的炎症。生物工程化的结肠特异性生态位通过多种免疫抑制途径触发自身反应性T细胞无反应性和极化促炎巨噬细胞，并阻止免疫细胞浸润到结肠固有层，促进上皮损伤的恢复。生物工程利基还可以预防与结肠炎相关的结直肠癌，并消除由激酶抑制剂和免疫检查点阻断引发的免疫相关结肠炎。