To address the role of Tpl2, a MAP3K8 that regulates innate/adaptive immunity 
and inflammation, in intestinal tumorigenesis, we crossed a Tpl2 KO allele into 
the Apc(min/+) genetic background. Here, we show that Apc(min/+)/Tpl2(-/-) mice 
exhibit a fivefold increase in the number of intestinal adenomas. Bone marrow 
transplantation experiments revealed that the enhancement of polyposis was 
partially hematopoietic cell-driven. Consistent with this observation, Tpl2 
ablation promoted intestinal inflammation. IL-10 levels and regulatory T-cell 
numbers were lower in the intestines of Tpl2(-/-) mice, independent of Apc and 
polyp status, suggesting that they were responsible for the initiation of the 
enhancement of tumorigenesis caused by the ablation of Tpl2. The low IL-10 
levels correlated with defects in mTOR activation and Stat3 phosphorylation in 
Toll-like receptor-stimulated macrophages and with a defect in inducible 
regulatory T-cell generation and function. Both polyp numbers and inflammation 
increased progressively with time. The rate of increase of both, however, was 
more rapid in Apc(min/+)/Tpl2(-/-) mice, suggesting that the positive feedback 
initiated by inflammatory signals originating in developing polyps is more 
robust in these mice. This may be because these mice have a higher intestinal 
polyp burden as a result of the enhancement of tumor initiation.