The Role of IL37 in the pathogenesis of inflammatory bowel disease

Project description

IL37 is a novel anti-inflammatory cytokine which is reduced in the circulation of patients with auto-immune diseases, including inflammatory bowel disease (1). Human peripheral blood mononuclear cells are capable of producing IL37, and in particular the T cell subset (2). Aberrant helper T cell responses play a key role in the pathogenesis of IBD (3-5). Thus it is of paramount importance to understand the triggers for pro and anti-inflammatory cytokine production by T cell subsets of patients with inflammatory bowel disease.

This project will look at characterising IL37 production in different cell subsets in the blood and lamina propria of patients with inflammatory bowel disease. Cells will be isolated from peripheral blood and colonic biopsies. Following appropriate processing or digestion and stimulation, flow cytometry will be used to characterise immune cell subsets and their capacity to produce IL-37. Additionally, colonic biopsy samples will be collected and stored to create frozen sections for immunofluorescent staining. Concurrently, patient data on disease activity, medication use and response will be collected. Disease activity and response to currently available medications will be correlated with IL-37 production to assess whether this cytokine plays a role not only in pathogenesis of disease, but also response to immunomodulating medications.

1. Li Y, Wang Y, Liu Y, et al. The possible role of the novel cytokines IL-35 and IL-37 in inflammatory bowel disease. Mediators Inflamm 2014;2014:136329.
2. Rudloff I, Cho SX, Lao JC, et al. Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells. J Leukoc Biol 2017;101:901-911.
3. Bishu S, El Zaatari M, Hayashi A, et al. CD4+ tissue-resident memory T-cells expand and are a major source of mucosal tumor necrosis factor alpha in active Crohn’s Disease. J Crohns Colitis 2019.
4. Dige A, Stoy S, Rasmussen TK, et al. Increased levels of circulating Th17 cells in quiescent versus active Crohn’s disease. J Crohns Colitis 2013;7:248-55.
5. Hegazy AN, West NR, Stubbington MJT, et al. Circulating and Tissue-Resident CD4(+) T Cells With Reactivity to Intestinal Microbiota Are Abundant in Healthy Individuals and Function Is Altered During Inflammation. Gastroenterology 2017;153:1320-1337.e16.