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

Janneke 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.

Regulation of intestinal epithelial homeostasis by Cyclin Y

Stefan 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.

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.

Pieter Hindryckx © ECCO

For the 14^th edition of the ECCO Congress we return to the venue of the 2014 Congress: the Bella Center in the city of Copenhagen, Denmark.

The central theme of the 2019 Congress is “Research drives clinical care”, reflecting a well-balanced cocktail comprising the latest advances in basic and clinical research in IBD and their (potential) implications for daily clinical practice.  

Silvio Danese © ECCO

Dear ECCO friends,

While we wait a few more months for our ECCO Congress 2019 and are getting ready to face another cold winter, I would like to give you an update on the latest ECCO Initiatives for the meeting, which are the result of much hard work by all the ECCO Committees.

Anastasia N. Nicolaou © Anastasia N. Nicolaou

Cyprus

N-ECCO National Representative: Anastasia N. Nicolaou
Job Title: GI - IBD Nurse

What influenced your decision to apply for the role of N-ECCO National Representative for your country?
I work in a centre which sees a large number of IBD patients and therefore I felt the need to have a more active role. I have also applied for a PhD in a local university which has a research programme on IBD. 

Sweden

Name of group: Swedish Organisation for the Study of IBD
Number of active members: 45
Number of meetings per year: Two main meetings plus numerous project meetings
President and Secretary: 
        Pär Myrelid, President
        Franscesca Bresso, Secretary
National Representatives: 
        Ann-Sofie Backman
        Michael Eberhardson
Joined ECCO in:  2004
Incidence of IBD in the country (if available): 
0.64% prevalence

Serbia

Name of group: Serbian IBD Association - SIBDA
Number of active members: 230
Number of meetings per year: 
        Steering Committee meetings: 6 per year, 1 General Assembly per year
        Educational meetings: 2 meetings/workshops annually
        Patient relations meetings: 1 per year and on demand
President and Secretary: 
        Aleksandra Sokic Milutinovic, President
        Zoran Milenkovic, Secretary
National Representatives: Srdjan Djuranovic and Mirjana Cvetkovic
Joined ECCO in:  As an association from 2012; we have had National Representatives since the beginning of ECCO.
Incidence of IBD in the country (if available): 
Not available in this moment.