Approved Research

The role of Rab46 in immune-mediated inflammatory diseases

Lay summary

Inflammation is an essential defence mechanism by which the body tries to protect us from infection and injury. However, inappropriate inflammation, where the immune system is active long after the injury has gone, plays a role in many chronic diseases, including rheumatoid arthritis, psoriasis, urticaria and atherosclerosis. People, who are susceptible to chronic inflammation often, have more than one disease, which suggests there may be a common mechanism that triggers immune cells to act inappropriately.

Many immune cells contain special storage packages called granules, which rapidly release their contents upon stimulation (e.g. injury), in order to generate repair. Release of these contents is highly regulated but aberrant release is associated with many inflammatory-based diseases.  Rab46 is a new protein that we know plays important roles in the release of granular contents in cells that, like mast cells, respond rapidly to injury. In addition, variations in the Rab46 gene have been associated with diseases characterized by inflammatory conditions. Therefore, we aim to investigate the contribution of Rab46 to the release of contents from immune cells and determine if impairment of this protein is common in chronic inflammation.

Here, we will investigate Rab46 using a resource of genetic and health data from over 100,000 patients stored in the UK Biobank. Genetic analysis of thousands of patients, for example with rheumatoid arthritis, will inform us if variations in the Rab46 gene is common to inflammatory disease. These studies will provide us with data to determine if Rab46 is a target for the development of novel therapeutics and/or could be utilized as a diagnostic tool to measure the probability of acquiring chronic inflammatory diseases.