TNF-α regulates the expression of its TNFR2 receptor (4, 13), presumably to limit excessive signaling, but because SOCS3 limits TNFR2 upregulation in response to flagellin, delaying the negative feedback loop, IEC may transcribe more TNF-α to compensate, resulting in the chronic inflammation characteristic of IBD. Here, TNFRSF1B is linked to inflammatory bowel disease.