Determining the anti-inflammatory mechanism and therapeutic potential of WNT2B in colitis abstract WNT signaling has been shown to modulate inflammation, and has been linked to important disease…

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Nemours Foundation $719,124 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to determine the anti-inflammatory mechanism and therapeutic potential of WNT2B in colitis.

The research will establish how WNT2B from intestinal mesenchymal fibroblasts prevents colitis by testing the hypothesis that WNT2B signals non-canonically to negatively regulate NFKB and reduce IL-6-associated inflammation in the colon. The work will examine the interaction between WNT2B and NFKB signaling, assess impacts on innate immune cell recruitment, and evaluate whether increased WNT2B expression can decrease active colitis or prevent colitis development in human disease. The project builds on findings from human loss-of-function studies and mouse models showing that WNT2B loss of function results in increased colon inflammation and immune cell recruitment through IL-6 signaling.

The Nemours Foundation, doing business as Nemours Children's Hospital, Delaware, serves as the recipient and will perform the work at its Wilmington, Delaware location (UEI ETGMYV7CKAJ7). The award period runs through May 31, 2031.

Determining the anti-inflammatory mechanism and therapeutic potential of WNT2B in colitis abstract WNT signaling has been shown to modulate inflammation, and has been linked to important disease processes in the intestine including inflammatory bowel disease, but the effects of WNT signaling depends on the context of the interaction and the specific WNT ligands involved. Studying individual wnts has been a major barrier to the field, but we have identified humans with WNT2B loss of function (LOF) and have subsequently shown that WNT2B LOF results in increased colon inflammation, particularly through IL-6 signaling, and increased immune cell recruitment in humans and mice. The overarching goal of this proposal is to determine how WNT2B functions to prevent colitis. We will test the novel hypothesis that WNT2B from intestinal mesenchymal fibroblasts signals non-canonically and negatively regulates nfκb to prevent IL-6 associated inflammation in the colon, so that increasing WNT2B is beneficial in human colitis. Furthermore, we will examine how WNT2B interacts with nfκb signaling to impact inflammation and whether there is a negative feedback relationship. The impacts of WNT2B on innate immune cell recruitment will also be assessed. Finally, we will evaluate whether WNT2B holds potential as a therapeutic target for human colitis by testing whether increased expression of WNT2B can either decrease active colitis or prevent the development of colitis.