The regulation and function of epithelial Glutathione Peroxidase 4 in Inflammatory Bowel Disease  

Timon Adolph © Timon Adolph

Aim of Research

Glutathione peroxidase 4 (GPX4) controls a specialised regulated form of cell death termed ferroptosis. Research supported by this ECCO Grant aims at investigating the regulation and function of GPX4 in intestinal epithelial cells (IECs) from patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC). This project aims to establish a role for ferroptosis and lipid peroxidation in IBD and to clarify the function of GPX4 in Crohn’s Disease.

Using exosomes to gain insights into the early phase of Crohn’s Disease  

Sare Verstockt © Sare Verstockt

Aim of Research

Crohn’s Disease (CD) is characterised by chronic inflammation of the gut. Treatment usually involves drug therapy or surgery with the goal of reducing inflammation and inducing and maintaining steroid-free remission and mucosal healing. A more intensive treatment early in the disease course leads to better outcomes. However, the time between symptoms and diagnosis is often years.

The aims of this project are to identify (a) the triggers present at the onset of CD, allowing (pointers for) new therapies, and (b) molecular markers that can help diagnose CD as early as possible. Given that exosomes provide a rich genetic profile reflecting their cellular origin, we are focussing on exosomal markers.

Innate lymphoid cells in Paediatric Inflammatory Bowel Disease  

Aline van Acker © Aline van Acker

The incidence of paediatric IBD (PIBD) is on the rise. However, the underlying aetiology of PIBD remains largely unknown, indicating the dire need for more knowledge on the mechanisms driving this disease. Innate lymphoid cells (ILCs) constitute an important component of the mucosal immune system. Recent years have seen an increase in ILC knowledge, with numerous publications highlighting the importance of ILCs in murine and adult IBD development and progression.

In this project, we aim to elucidate ILC heterogeneity and function specifically in PIBD. In practice, single-cell suspensions are isolated from blood and colon biopsies of PIBD and non-PIBD patients admitted to the Paediatric Gastroenterology, Hepatology and Nutrition Unit at Karolinska University Hospital, Stockholm, Sweden or the Department of Clinical Research and Education at Södra Hospital, Stockholm.

Francesca Maria Onidi © Francesca Maria Onidi

The award of an N-ECCO Travel Grant, organised by ECCO, enabled me to spend time as an intern in the prestigious Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, the largest IBD centre in Italy. The Centre provides the most innovative treatments and therapeutic strategies for IBD patients in accordance with current scientific evidence and offers a multidisciplinary approach to IBD with the help of industry experts and novel technologies. At the Humanitas outpatient clinic dedicated to IBD, patients are followed by IBD nurse Simona Radice. In addition to the provision of medical assistance to patients, the Centre is strongly engaged in research activities aimed at developing new treatments and diagnostic and/or therapeutic strategies. Participation in clinical trials is subject to a preliminary clinical evaluation during a specialist visit to the Centre.

The role of Nlrp9b in regulating intestinal inflammation  

Danping Zheng © Danping Zheng

Aim of the research

Innate immune signalling pathways, including inflammasome-forming Noll-like receptors (NLR), are thought to mediate the risk of Inflammatory Bowel Disease (IBD) since this system acts as the first line of defence in the recognition of enteric pathogens. In our preliminary study, we identified a new NLR member, Nlrp9b, whose role in the pathogenesis of IBD remains to be clarified. The aim of our study is to investigate the role of Nlrp9b in regulating intestinal inflammation and the underlying mechanisms.

TSG-6, a potential new therapeutic target in fistulising Crohn’s Disease  

Sudharshan Elangovan © Sudharshan Elangovan

Background

Fistulising Crohn’s Disease (CD) represents a demanding, complex, and as yet unresolved issue, characterised by lesions with active pus drainage through the external fistula openings. Despite advances in understanding of the pathophysiology, to date there are no specific and efficient therapies or molecular markers for its treatment or prevention. TNF-α stimulated gene/protein-6 (TSG-6), an anti-inflammatory protein produced in response to signals from injured tissue, has been shown to exert remarkable therapeutic effects on colitis and on wound healing in various disease models.

Monocyte-derived macrophages as crucial players in the resolution of inflammation and tissue repair in Inflammatory Bowel Disease  

Sales Ibiza © Sales Ibiza

Background

Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract leading to debilitating symptoms. No curative therapies are currently available for IBD, with the consequence that the disease has a significant impact on the emotional, financial and social status of patients and their families. Although most studies conducted on IBD over the past few decades have investigated abnormal adaptive immunity, the focus has recently shifted towards alterations in innate immune response. Recent data suggest a causal link between defects in the resolution of inflammation associated with impaired bacterial clearance, excessive cytokine secretion and altered monocyte-macrophage (Mφ) transition in patients with IBD.

Deciphering the gut-specific B cell response in Inflammatory Bowel Disease (IBD)  

Mathieu Uzzan © Mathieu Uzzan

Aim of the research

Given that there is a large complement of mucosal B cells that plays a pivotal role in the regulation of the microbiome and in mucosal homeostasis, it is likely that they play an important but yet understudied role in the pathogenesis of IBD. Therefore, we hypothesize that mucosal inflammation as seen in IBD will induce a B cell response with homeostatic and perhaps pathogenic properties.

Investigation of the role of Par4-associated cell polarity and associated barrier defects in Inflammatory Bowel Diseases  

Federica Branchi © Federica Branchi

Aim of the research

In Inflammatory Bowel Diseases (IBD), epithelial barrier defects occur as a consequence of chronic inflammation. Recent research has suggested that cell polarity alterations may be upstream of barrier defects and additionally play a role in IBD-associated carcinogenesis (colitis-associated and small intestinal carcinoma). Par4 is a gene encoding a protein crucial in the development of cell polarity. LKB1, its human homologue, is mutated in Peutz-Jeghers syndrome (PJS), a genetic condition characterised by a higher risk of epithelial cancers. Considering the pivotal role of Par4/LKB1 in the development of epithelial cell polarity, this project aims to assess its involvement in IBD-associated barrier defects and carcinogenesis.

Janneke van der Woude © ECCO

During the ECCO’18 Vienna Congress the Scientific Committee cordially welcomed Michael Scharl and Sebastian Zeissig as new members.