Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease

What is it about?

Patients with inflammatory bowel disease (IBD) have lifelong complications with their digestive tract as well as issues such as bone loss and increased risk of fracture. Current treatments for IBD all aim to mitigate disease symptoms, but most come with negative side-effects like increased risk of serious infections. Here we characterize a novel pathological adaptation in the gut, where we see abnormal lymphatic vessels (important for transporting excess fluid and components from the immune system away from tissues) develop, in association with increased levels of proteins typically found in inflammatory conditions. We identified alterations in bone turnover in IBD animals as well, with similar inflammatory changes observed in the bone as was seen in the gut. Therefore, we found these two tissue beds are driven by similar immunological states in their pathological development in chronic gut inflammation. Finally, we examined the beneficial impact of irisin treatment, a factor that is naturally released into circulation during exercise. We found irisin treatment resolved and restored both gut and bone changes observed during the disease. In summary, our data indicate analogous inflammatory states driving pathology in the gut and a distant site (i.e. bone) during chronic IBD. Additionally, we discovered irisin treatment successfully improves the IBD pathology in both tissue sites, providing a new, holistic therapeutic which may be beneficial to patients suffering from IBD.

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