New research project could help to develop treatments for people with Crohn’s disease or other intestinal diseases, by identifying what molecules macrophages produce that support gut lining development.
Our gut lining is made up of many different cells – Goblet cells produce mucus, enteroendorcine cells produce hormones and Paneth cells release antimicrobial products such as lysozymes and defensins, which help to protect the gut from infections.
All of these cells develop from intestinal stem cells, which can produce all the cells that make up the gut lining when they divide. Paneth cells are found next to these stem cells and release a molecule that helps to keep them alive and protect them from infections. When Paneth cells are lost, the intestinal stem cells are also lost, which in turn affects the development of the gut lining.
Previous work by Professor Neil Mabbott of The Roslin Institute has shown that macrophages (a type of white blood cells which help to fight infection) found in the gut play an important role in maintaining the function of Paneth cells.
If macrophages are changed or reduced, for example by blocking an important receptor that controls their growth, that can also affect the function of Paneth cells and influence the development of the gut.
A reduction or change in the function of Paneth cells is seen in Crohn’s disease patients with small intestinal problems and this may be due to poor support from macrophages.
Neil Mabbott has been awarded £520K by the Medical Research Council to investigate the role macrophages play in the maintenance of Paneth cells and intestinal stem cells.
The study aims to discover what molecules the macrophages produce to maintain the health of Paneth cells and intestinal stem cells. The final part of the study will hopefully determine whether the negative effects of a reduction in macrophages on intestinal development can be restored with novel treatments.
The research, which will run for three years, could ultimately help to develop treatments for people with Crohn’s disease or other intestinal diseases.
An understanding of how macrophages support intestinal crypts may help develop new therapeutics to treat certain intestinal diseases associated with disturbances to Paneth cells and intestinal stem cells.
Professor Neil Mabbott, The Roslin Institute