The intestine holds up to 70% of the body’s immune cells across a surface area of 32 square meters, yet it must tolerate friendly gut microbes while attacking harmful ones. When this balance breaks down, it drives inflammatory bowel disease (IBD), which affects millions worldwide. Up to 40% of patients do not respond to existing generic immunosuppressants. This research directly maps the molecular pathways that go wrong in human intestinal immunity, using large clinical cohorts that include patients with complex, drug-resistant complications. The work is fundamentally about understanding how the intestinal immune system functions in health and how it becomes dysregulated in disease. If successful, it will inform the design of new, targeted therapeutics for IBD, moving beyond the current one-size-fits-all immunosuppression. This is translational fundamental science: it aims to turn a deep understanding of human tissue immunology into better treatments for immune-mediated inflammatory disorders, potentially improving outcomes for the millions of patients who currently have limited options.
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The intestine is a major immune organ, housing up to 70% of the body’s immune cells and incorporating a luminal surface area of about 32 square meters. The intestine must balance its role in absorption of nutrients with optimal immune function. The intestinal immune system must co-exists symbiotically with luminal microbes whilst eliminating harmful pathogens to prevent these from entering the blood and lymph circulatory systems. Disturbance in intestinal immunity contributes to a variety of conditions including inflammatory bowel disease (IBD), cancer and aging. IBD affects several million people world-wide and up to 40% patients fail to respond to available, largely generic immunosuppressant medication. In IBD intestinal immunity is dysregulated leading to destruction of normal intestinal cellular physiology and function. We develop or optimise state of the art technologies and apply these to define molecular pathways governing human intestinal immune health and IBD. We take advantage of our large clinical cohorts to directly map human intestinal pathology in all sub forms of the disease including patients with complex drug resistant complications. This information is used to inform design of novel therapeutics to improve management of this condition. Our work contributes to the broader aim of the MRC Translational Immune Discovery Unit to define human tissue and barrier immunology and its dysregulation in a variety of immune mediated inflammatory disorders.
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