An Injectable Subcutaneous Colon-Specific Immune Niche For The Treatment Of Ulcerative Colitis
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 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 colons 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. O_FIG O_LINKSMALLFIG WIDTH=142 HEIGHT=200 SRC="FIGDIR/small/560652v1_ufig1.gif" ALT="Figure 1"> View larger version (86K): org.highwire.dtl.DTLVardef@127151aorg.highwire.dtl.DTLVardef@da6ce9org.highwire.dtl.DTLVardef@246ee1org.highwire.dtl.DTLVardef@1eb801b_HPS_FORMAT_FIGEXP M_FIG C_FIG