Deciphering the role of plasmacytoid dendritic cells in gut-associated lymphoid tissues during homeostasis and Crohn's Disease

Urs Mörbe  © Urs Mörbe

Background & aim of research

Inappropriate intestinal immune responses can result in Inflammatory Bowel Diseases (IBD), such as Crohn’s Disease (CD), that require lifelong treatment or surgery. While it is now well understood that T cells are a key driver of pathogenic intestinal immune responses during CD, the underlying molecular mechanisms and roles of other local immune cells remain incompletely understood. Interestingly, previous studies have shown that plasmacytoid dendritic cells (pDC) are potent modulators of immune cell responses and are enriched in the mucosa of IBD patients. However, their precise role remains unclear. This study aims to clarify the distribution and roles of pDC during health and CD.

Identification of markers to predict post-operative disease recurrence in Crohn's disease.

Annemarie de Vries © Annemarie de Vries

Alison Simmons © Alison Simmons

Background & aim of research

Ileocolonic resection (ICR) remains an important modality in the treatment of ileal or ileocolonic Crohn’s disease (CD)1,2. However, surgery is not curative and post-operative recurrence after ICR is common, with regard to clinical symptoms, endoscopy and need for re-resection2,3. To prevent post-operative recurrence, current guidelines advise to start prophylactic medication in patients at high risk4–6. Identification of these patients remains a challenge, despite clinical and histologic risk-stratification. The main aim of this study is to identify new biomarkers to predict endoscopic disease recurrence in a prospective cohort of CD patients who undergo ICR.

Early prediction of treatment response in children with Inflammatory Bowel Disease with intestinal ultrasound

Elsa van Wassenaer © Elsa van Wassenaer

Background & aim of research

Childhood-onset IBD is known for its more complicated disease course. Studies have established that achieving remission at an early stage of disease improves long-term prognosis. Therefore, choosing the right treatment for children with IBD in the early stages of disease is key to preventing disease progression and to altering the disease course. Intestinal ultrasound (IUS) is a promising non-invasive tool for IBD, but its potential for early prediction of treatment response has not yet been explored in the paediatric population. Therefore the aim of the RAINBOW-3 study is to evaluate, in children with IBD (new-onset or known), the predictive value of IUS at week 6 of treatment for treatment response at week 13.

The PTPN2 loss-of-function variant as predictor of therapeutic response to JAK inhibitor therapy in IBD

Marianne R. Spalinger © Marianne R. Spalinger

Raja Atreya © Raja Atreya

Background & aim of research

JAK inhibition has emerged as a promising novel therapeutic strategy in IBD. However, only a subgroup of patients responds to JAK inhibitors and there are currently no predictive markers available that predict sustained response. Our recent work strongly indicates that loss-of-function variants in the PTPN2 gene might serve as predictive markers for therapeutic effectiveness, and the main goal of this project is to define whether PTPN2 dysfunction can serve as a predictor for efficacious JAK inhibitor therapy.

Caring and management of patients with Inflammatory Bowel Disease: a focus on specialist nursing interventions

Rosanna Irene Comoretto © Rosanna Irene Comoretto

Background & aim of research

The number of specialist nurses dedicated to the care and management of patients with Inflammatory Bowel Disease (IBD) is increasing across Europe, and their role is widening. Despite the increased interest in the opportunities associated with this emerging healthcare professional role, from the perspectives of both patients and clinicians, scarce evidence is available on the effectiveness of specialist nursing interventions. An in-depth review of the impact of specialist nursing interventions on the care and management of patients with IBD, and especially on the health-related quality of life (QoL), is needed.

The main outcome of interest in this context is clinical remission (the proportion of patients in whom remission is achieved or maintained). Additional outcomes are: the proportion of hospital admissions/readmissions, the length of hospital stay, clinical improvement, patients’ QoL and the effectiveness of treatment.

Defining the Role of invariant Natural Killer T (iNKT) Cells in Perianal Fistula 

Sulak Anandabaskaran © Sulak Anandabaskaran

Background & aim of research

Perianal fistulising Crohn’s Disease (pCD) is associated with poor outcomes and impaired quality of life. It remains difficult to manage despite medical and surgical advancements, likely due to poor understanding of the underlying immunology. Previous multiparameter flow cytometry work in our lab on immune cells isolated from peripheral blood and fistula curettage samples showed expansion of iNKT cells in perianal fistula compared to peripheral blood. Furthermore, iNKTs have been suggested to have a potential role in key processes in fistula pathogenesis, namely epithelial-to-mesenchymal transition and extracellular matrix degradation. The role of iNKTs in inflammation remains poorly defined and their function in human IBD is largely unexplored. Therefore, in this experiment we aim to further define their role in the pathogenesis of perianal fistula.

Intestinal epithelial cell stress modulates enteric fibroblastic and neuronal profiles in Inflammatory Bowel Disease

Celia Escudero-Hernández  © Celia Escudero-Hernández

Background & aim of research

Genetic studies have implicated the autophagy gene ATG16L1 and the endoplasmic stress (ER) gene XBP1 in the pathogenesis of Inflammatory Bowel Disease (IBD). Indeed, spontaneous inflammation develops in mice lacking ATG16L1 or XBP1 expression in intestinal epithelial cells (IEC). Because of the dominant role of failing autophagy and ER stress in IBD, we hypothesise that IEC stress contributes to intestinal fibrosis, gut dysmotility and pain during colitis.

This project aims, for the first time, to thoroughly comprehend the role of crucial IBD epithelial stress factors (i.e. ATG16L1 and XBP1 impairments) in enteric fibroblasts and neurons and to explore potential future intervention points.

Decoding the neuroimmune crosstalk in Inflammatory Bowel Diseases

Silvia Cerantola © Silvia Cerantola

Background & aim of research

Inflammatory Bowel Disease (IBD) results from an anomalous interaction between genetic, environmental, immunoregulatory and microbial-derived factors. IBD- associated specific mutations include genes involved in microbial recognition, such as mutations in the Toll-like receptor 4 (TLR4). Beside controlling host defence responses, TLR4 modulates enteric nervous system (ENS) activity, gut motility and repair processes following an insult. TLR4 deficiency in mice leads to significant ENS alterations, characterised by modified gut motility and susceptibility to inflammation. The findings of decreased gut catecholamine levels in IBD patients and the onset of milder experimental colitis after sympathectomy highlight the role of the nervous system as a key regulator of immune responses. Therefore, our research project aims to decode the neuroimmune interactions between the catecholaminergic system and innate immune sensor TLR4 in dinitrobenzene sulphonic acid (DNBS)-induced ileitis.

Deciphering the bioactive role of extracellular matrix fragments (matrikines) in Crohn's Disease (CD) fibrostenosis as potential therapeutic targets and biomarkers

Margarita Papatheodoridi © Margarita Papatheodoridi

Background & aim of research

We have pioneered in studying ex vivo extracellular matrix (ECM) remodelling, which is known for its key role in Crohn’s Disease (CD) fibrostenosis. By adding disease-relevant enzymes on the ECM of CD patients’ intestine, we identified numerous matrikines (specific ECM peptide fragments) unique in CD fibrostenosis. Peptidomics software analysis showed specific likelihood for bioactivity for 19 of those matrikines (Giuffrida et. al, unpublished data) ().

This project aims to explore the bioactivity of matrikines in CD fibrostenosis in vitro.

Examining a novel sulphide-reducing diet As Therapy in Ulcerative Colitis (EAT-UC trial)

Robert V. Bryant © Robert V. Bryant

Background & aim of research

It is currently unknown whether diet influences inflammation in Ulcerative Colitis (UC). Observational and experimental data suggest that modulating sulphide within the luminal environment may have therapeutic potential for UC. The aim of this trial is therefore to determine whether a sulphide-reducing diet, designed to attenuate excess microbial production of potentially noxious gases in the colon, can induce remission in UC.