The role of mononuclear phagocytes in gut mucosal healing following inflammation
Final Report Abstract
Inflammatory bowel disease (IBD) is a group of chronic, relapsing diseases characterized by recurring idiopathic inflammation of the gastrointestinal tract. Clinical symptoms include abdominal pain, rectal bleeding, weight loss, fever and diarrhoea. Patients who have undergone complete mucosal healing after initial disease symptoms, presented less subsequent overall disease activity and risk of surgery. Therefore, achieving mucosal healing is an attractive therapeutic strategy to treat IBD patients. The immune system plays a critical role in the process of mucosal healing, with T cells and myeloid cells being the most studied cell types. During the DFG Research fellowship “The role of mononuclear phagocytes in gut mucosal healing following inflammation” we investigated the temporal dynamics of immune cells during intestinal inflammation and recovery in a murine model of experimental colitis. We found that while mononuclear phagocytes (the initial cells of interest in this project) expand only slightly during recovery, B cells are the dominant cell type specifically increasing in numbers during tissue repair. B cells with their dual role in the mucosal immune system as antigen presenting cells and antibody secreting cells, might be more important for intestinal homeostasis than previously thought. In this project, we found that increasing numbers of B cells are located in tertiary lymphoid structures, which expanded in number and size. While the B cells were predominantly IgM+ IgD+ mature naïve B cells, using scRNA sequencing we revealed a previously undescribed subpopulation during intestinal tissue repair which we aim to further characterise. Importantly, our data shows that depletion of B cells during the recovery phase using the CD19cre x iDTR mouseline, resulted in an upregulation genes associated with collagen catabolic processes as well as a downregulation of pro-inflammatory cytokines, suggesting that removal of B cells might improve tissue repair. In the further course of this project we aim to validate the above described results and further investigate the molecular mechanism how B cells might be involved in tissue regeneration. Overall, the results of this project, once published in a scientific journal, might help to shed light on the previously described ambiguous results on the role of B cells during IBD and might be of value for therapeutical approaches targeting mucosal healing and tissue repair.
Publications
- (2019). Liver X receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms
Parigi S.M., Das S., Frede A., Cardoso R.F., Tripathi K.P., Doñas C., Yoo H., Antonson P., Engstrand L., Gustafsson J.A., Villablanca E.J.
(See online at https://doi.org/10.1101/818369)
