To evaluate the direct effects of TL1A-DR3 signaling on fibroblasts in vivo in the context of experimental IBD, we generated Rag−/− mice with selective DR3-deficiency on fibroblasts (Rag−/−Dr3∆Col1a2) and induced TL1A-exacerbated colitis, as above. Here, TNFRSF25 is linked to inflammatory bowel disease.