Host defence peptides as novel modulators of autophagy in inflammatory bowel disease

Increasing numbers of patients are diagnosed with inflammatory bowel disease (IBD) each year, in the United Kingdom (UK) (~300,000) and worldwide. IBD can cause a variety of serious symptoms including weight loss, bloody diarrhoea, extreme tiredness and chronic pain. Many current treatments for IBD are designed to reduce inflammation and induce remission of the disease. However, these drugs are sometimes not effective, and those that are can diminish over time, with only ~30% of patients having long-term health benefits, and 10–35% of Crohn’s Disease (CD) (one of the two main forms of IBD) patients requiring surgery within a year of diagnosis and up to 61% by 10 years. It is therefore essential that new drugs are developed that target IBD at an early stage before the disease starts. A family of naturally occurring molecules called cathelicidins are a key part of the immune system in humans. Cathelicidins have powerful antibacterial properties and they can influence the outcome of an infection by altering the way the body responds to inflammation. Preliminary work has indicated that the human cathelicidin, LL-37, can stimulate autophagy, making them attractive prospects for developing new drugs for treating CD. We aim to understand how cathelicidins stimulate autophagy and investigate how they can be used to a) reduce the ability of AIEC to grow inside cells and b) dampen down damaging inflammation. We believe that with further research and better understanding, LL-37 could be used to stimulate autophagy, providing a powerful new approach to treating CD at an early stage before the disease takes hold, which will significantly improve the quality of life of patients.