ECCO Grant Study Synopsis: Urs Mörbe
Urs Mörbe, ECCO Grant Awardee
Deciphering the role of plasmacytoid dendritic cells in gut-associated lymphoid tissues during homeostasis and Crohn's Disease
© 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.
Methodology/experiments that will be used
We will use clinical resection material from IBD patients and non-inflamed control tissue donors to study pDC by flow cytometry, histology and single-cell RNA sequencing. By applying this multifaceted approach, we hope to shed light on the distribution and functions of these cells during health and their contributions to disease pathology.
Anticipated main impact
pDC have the capacity both to promote and to suppress intestinal immune cell responses and are enriched in the intestine of CD patients. However, their precise role during health and CD remains unknown. We anticipate closing this knowledge gap and are confident that we will be able to conceptually advance our fundamental understanding of intestinal immune (dys-)regulation during CD. By deciphering molecular pathways and interactions that drive inflammation, generated results could potentially help in the future design of novel pharmacological intervention strategies against CD.
Experiments and analyses are currently underway and our efforts during the coming months will focus on the recruitment of further CD patients and the mining of our RNA sequencing datasets to discover dysregulated signalling pathways that could contribute to disease pathology.