Project Details
Projekt
The role of mononuclear phagocytes in gut mucosal healing following inflammation
Applicant
Annika Frede, Ph.D.
Subject Area
Immunology
Term
from 2017 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 391137920
Inflammatory bowel disease (IBD) is a group of chronic, relapsing diseases characterized by recurring idiopathic inflammation of the gastrointestinal tract followed by remission. Clinical symptoms include abdominal pain, rectal bleeding, fever and diarrhea. It is estimated that 3 million people in Europe are affected and the incidence is increasing. Despite the knowledge about several factors involved in the pathogenesis of IBD the etiology is not fully understood and no curative therapies are available. Different studies concerning IBD reveal a strong association between mucosal healing and improved patient prognosis, therefore the induction or amplification of mucosal healing can be regarded as a novel therapeutic strategy. Up to date, the mechanisms to induce tissue repair and regeneration are still poorly understood. Mononuclear phagocytic cells, including monocytes, dendritic cells (DCs) and macrophages, were described to promote innate and adaptive immune responses and are instrumental for the maintenance of intestinal homeostasis. The role of these cell populations during the mucosal healing process has not yet been described in detail. Preliminary data from the host laboratory demonstrate that monocytes and macrophages are highly recruited to the colon during tissue regeneration, after dextran sodium sulphate (DSS) - induced colitis, suggesting a critical role in mucosal healing. Furthermore, frequencies and numbers of different DC populations in the intestine undergo significant changes during intestinal inflammation. DCs are key players in immune regulation and tolerogenic DCs are of high importance in maintaining homeostasis in the gut. However, if DCs play a role during tissue regeneration was not yet described. This projects aims to unravel the mechanism behind mucosal healing and interrogate the potential of mononuclear phagocytes in inducing or improving mucosal healing after intestinal inflammation. Different monocyte and macrophage as well as DC populations involved in mucosal healing shall be phenotypically and functionally characterized. The aims of this project are to identify cell subpopulations which influence the process of mucosal healing and how mucosal healing is induced after inflammation in general. Furthermore, the influence of different bacterial species on the tissue repair process shall be analyzed and especially the role of bacterial compounds on the ability of macrophages and DCs to induce or improve mucosal healing.
DFG Programme
Research Fellowships
International Connection
Sweden
