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Two articles from the Kennedy Institute review the latest in understanding immune control in the gut and skin and explain how this knowledge is being translated into new treatments for inflammatory disease

Progress in targeting inflammatory disease in the gut and skin
Human gut tissue analysed using fluorescent RNAScope. Image credit: Dr Sam Bullers, Powrie lab

The gut, skin and other so-called barrier surfaces offer first line defense against exposure to the environment and harmful microbes. In two review articles, published in Nature Immunology and Immunity, Professor Fiona Powrie's group examine key cells types and molecular cues that control the immune system at barrier surfaces, a number of which are emerging as therapeutic targets in inflammatory bowel disease (IBD).

Dr. Natasha Whibley, who co-authored the Nature Immunology review says, "Regulatory T (Tregs) are tasked with limiting unnecessary immune activation throughout the body. Our review discusses the emerging theme that Tregs are uniquely adapted to barrier sites, such as the intestine and skin, where they display novel features that go beyond their classical role in suppression of inflammatory responses".

Defective Treg responses at barrier sites are associated with several chronic inflammatory diseases, such as IBD and atopic dermatitis. These diseases remain a major challenge to treat, therefore, increased understanding of barrier site Tregs is needed to better guide therapies.

The review published in Immunity examines the current and potential use of therapies that target immune molecules called cytokines in IBD. Cytokines are produced by many different cell types in the immune system that have far ranging biological effects, including control of inflammation.

Fiona says, "There has been tremendous progress in the field, and the introduction of therapies that target the cytokine TNF have transformed the treatment of IBD. However, many patients do not respond to these treatments, and relapse or flares are common. Our review examines the dynamic regulation of well-known and emerging cytokine networks in subsets of patients and at different stages of disease. More research in this area will facilitate personalised medicine approaches to IBD to improve patient outcomes".

The Immunity review was commissioned as part of the journal's 25th Anniversary Special Issue focused on cytokines and their role in health and disease. Notably, some of the first studies linking cytokines to intestinal inflammation were published by Fiona's group more than two decades ago.