Grant: Project Grant

Inflammatory bowel disease (IBD) affects about 1/140 Canadians and is becoming increasingly common. Current treatments for IBD work in many people, but are not curative and frequently have difficult side effects. One promising approach to treating IBD is cellular therapy-using patients' own "suppressor" white blood cells to reduce inflammation specifically in the gut without affecting the rest of the immune system. Our project will focus on one type of suppressor cells, Tr1 cells. We have published that Tr1 cells have unique properties that reduce unwanted inflammation and may help the function of the cells that line the gut (epithelial cells). We also found that Tr1 cells can help treat inflammation in two mouse models of IBD. We will expand on these findings to help determine how Tr1 cells may be used to treat IBD. In aim 1, we will test whether Tr1 cells can prevent inflammation in an established spontaneous mouse IBD model and examine how this occurs. In aim 2, we will test Tr1 cells in a common model of chemically induced colitis to focus on prevention and repair of gut injury. In aim 3, we will use a recently developed technology to make Tr1 cells respond specifically to a bacterial protein in the gut, and test whether this improves their ability to treat IBD in our models. Finally, in aim 4, we will use human colonic organoids ("mini-guts" grown from intestinal biopsies from volunteers) and Tr1 cells (purified from blood) to determine how Tr1 cells protect the human gut from inflammatory injury and may help to repair it. If successful, this project will allow us to develop protocols to isolate, expand, and transfer Tr1 cells into volunteers to determine their safety and effectiveness against IBD.