SciCom
11December2018

ECCO Grant Study Synopsis: Janneke N. Samsom

Janneke N. Samsom, ECCO Grant Winner

TIGIT+CD38+ effector cells: New players in suppressing inflammation in IBD?

 

03 SciCom 5 5 Samson Janneke MASTER ECCO Grant synopsisJanneke N. Samsom 
© Janneke N. Samsom 

Background and Hypothesis

In Inflammatory Bowel Disease (IBD), T-cell reactivity against harmless microbial antigens drives chronic inflammation. After induction of remission, patients receive T-cell-suppressing maintenance treatment, which is effective in maintaining remission in some patients but not others. “T-cell immunoglobulin and ITIM domain” (TIGIT) is a novel inhibitor of T-cell activation. Preliminary experiments show that human circulating TIGIT-expressing CD38+ effector T cells are concomitantly enriched in the inhibitory molecules IL-10, PD-1 and CTLA-4. Crucially, frequencies of these cells were much reduced in a subgroup of paediatric IBD patients at disease onset and associated with reduced duration of clinical remission during follow-up.

We hypothesise that TIGIT+CD38+ effector T cells are functionally involved in immune regulation of microbial responses in the gastrointestinal tract.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

11December2018

ECCO Grant Study Synopsis: Stefan Koch

Stefan Koch, ECCO Grant Winner

Regulation of intestinal epithelial homeostasis by Cyclin Y

 

03 SciCom 4 4 Koch Stefan MASTER ECCO Grant synopsis roundedStefan Koch
© Stefan Koch

Aim of Research

Genetic predisposition contributes to the development of Inflammatory Bowel Diseases (IBD). Prior GWAS studies have identified numerous IBD risk loci, but most of them have no assigned function to date. The aim of this study is to explore the role of the IBD risk gene CCNY, encoding the Wnt signalling activator Cyclin Y, in intestinal homeostasis and wound repair.

Because Wnt signalling is essential for the maintenance of intestinal epithelial stem cells, we anticipate that CCNY mutations impair intestinal Wnt signalling and thereby reduce epithelial regeneration during colitis.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

11December2018

ECCO Grant Study Synopsis: Timon Adolph

Timon Adolph, ECCO Grant Winner

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

 

03 SciCom 3 3 Adolph Timon MASTER ECCO picture roundedTimon 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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

11December2018

ECCO Grant Study Synopsis: Sare Verstockt

Sare Verstockt, ECCO Grant Winner

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

 

03 SciCom 2 2 Verstockt Sare MASTER ECCO Grant synopsis rounded 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.

 

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

11December2018

ECCO Grant Study Synopsis: Aline van Acker

Aline van Acker, ECCO Grant Winner

Innate lymphoid cells in Paediatric Inflammatory Bowel Disease  

 

03 SciCom 1 1 Van Acker Aline Photo roundedAline 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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

04October2018

N-ECCO Travel Award Report

Francesca Maria Onidi, N-ECCO Travel Awardee 2018

03 SciCom 4a MASTER Francesca Onidi
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.

Posted in ECCO News, SciCom, Committee News, N-ECCO, Volume 13, Issue 3

04October2018

ECCO Fellowship Study Synopsis: Danping Zheng

Danping Zheng, ECCO Fellow 2018

The role of Nlrp9b in regulating intestinal inflammation  

 

03 SciCom 5a MASTER Danping Zheng
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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 3

04October2018

ECCO Fellowship Study Synopsis: Sudharshan Elangovan

Sudharshan Elangovan, ECCO Fellow 2018

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

 

03 SciCom 3a MASTER Sudharshan Elangovan
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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 3

04October2018

ECCO Fellowship Study Synopsis: Sales Ibiza

Sales Ibiza, ECCO Fellow 2018

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

 

03 SciCom 2a MASTER Ibiza Martinez Sales image
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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 3

04October2018

ECCO Fellowship Study Synopsis: Mathieu Uzzan

Mathieu Uzzan, ECCO Fellow 2018

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

 

03 SciCom 6a MASTER Mathieu UzzanMathieu 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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 3

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