An Injectable Subcutaneous Colon-Specific Immune Niche For The Treatment Of Ulcerative Colitis

Abstract

AbstractAs 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 nanofibers 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.