ECCO Fellowship Study Synopsis: Sales Ibiza
Sales Ibiza, ECCO Fellow 2018
Monocyte-derived macrophages as crucial players in the resolution of inflammation and tissue repair in Inflammatory Bowel Disease
 Sales Ibiza © Sales Ibiza |
Background
Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract leading to debilitating symptoms. No curative therapies are currently available for IBD, with the consequence that the disease has a significant impact on the emotional, financial and social status of patients and their families. Although most studies conducted on IBD over the past few decades have investigated abnormal adaptive immunity, the focus has recently shifted towards alterations in innate immune response. Recent data suggest a causal link between defects in the resolution of inflammation associated with impaired bacterial clearance, excessive cytokine secretion and altered monocyte-macrophage (Mφ) transition in patients with IBD.
Aim of research
Our preliminary data indicate that resolution of inflammation during Colitis is dependent on a specific subpopulation of monocyte-derived macrophages with a pro-resolving phenotype. Therefore, the main goal of our project is to clarify the functions of these pro-resolving macrophages during intestinal inflammation and to investigate the differentiation pathways favouring their pro-resolving phenotype. Unraveling macrophage polarisation mechanisms during Colitis will elucidate the pathways of inflammation resolution, representing a major breakthrough in understanding of the pathogenesis of IBD, and will be of crucial importance for the development of novel therapeutic strategies in the fight against IBD.
Methodology
In the first phase of our project, we will investigate the timing and the phenotypical changes that occur during monocyte differentiation in Colitis using in vivo Mφ-specific genetic tracing and loss-of-function studies in pro-resolving Mφs. In the second phase, we aim to translate our findings to the clinical setting by studying the possible contribution of pro-resolving Mφs in the pathogenesis of IBD. To this end, the phenotype and pro-resolving properties of intestinal Mφs will be studied in IBD patients during acute disease and in remission compared to healthy controls.