A model for regulation of TNF-α-induced apoptosis in the intestine.

<p>(A) Regulation of TNF-α response in the wild-type duodenum. In this context, resident T-cells promote MCP-1 expression by epithelial goblet cells. This MCP-1 functions to restrict pDC recruitment to the lamina propria. In the absence of pDCs, apoptosis induced by exogenous TNF-α is relatively low. Neutralization of MCP-1 in wild-type animals results in recruitment of pDCs and enhanced TNF-α-induced apoptosis. (B) Regulation of TNF-α response in the Rag1 null duodenum. The lack of intestinal T cells in Rag1 mice leads to a reduction in MCP-1 expression by goblet cells, allowing for recruitment of pDCs to the lamina propria. These pDCs influence the activation state of TNF-α-induced signaling pathways in epithelial cells, ultimately resulting in enhancement of TNF-α-induced apoptosis. Ablation of pDCs in Rag1 null mice restores the signaling network, and therefore the response to TNF-α, to a wild-type state. (Note, the cell surface markers used to identify each of the relevant immune cell types is specified.)