On Thursday 23 June 2022, Line Wulff will defend her PhD thesis "Heterogeneity in Human Intestinal Mononuclear Phagocytes".
Time: 13:00
Place: Bldg. 303A, auditorium 45
& Zoom https://dtudk.zoom.us/meeting/register/u5Ird-yvqz8sE9V-Em8CO58ildiiBC2TxNEz
Please be aware that the PhD defense may be recorded - This will also be informed at the beginning of the PhD defense.
Supervisor: Professor William Agace
Co-Supervisor: Associate Professor Lars Rønn Olsen
Members of assessment committee:
Professor Susanne Brix, DTU Bioengineering
Professor Muzlifah Haniffa, University of Newcastle
Professor Frode Lars Jahnsen, University of Oslo
Chairperson:
Associate Professor Katharina Lahl, DTU Health Tech
Abstract:
The intestine is the biggest surface of the human body exposed to the external environment. It runs as tube through the body and has essential tasks in absorption of nutrients and vitamins from ingested food. The small intestine (SI) takes care of the major parts of nutrient absorption and its’ environment reflects this. The colon is home to billions of bacteria, fungi and virus forming the microbiome, which have been shown to be important in both health and disease. Due to the heavy load of foreign compounds in both SI and colon, the intestinal tissues are the biggest reservoir if immune cells in the body. These cells have to simultaneously remain alert to infectious challenges while not create unwanted inflammation towards harmless compounds. When this balance is disrupted disease such as food allergy and chronic inflammatory bowel diseases can arise. This PhD project have unbiasedly studied a specific group of immune cells referred of as mononuclear phagocytes as these are important in the initiation long-term immune responses and thus are proposed to be important in both health and disease. The lack of appropriate techniques have previously hindered isolation of the individual gut associated tissues and thus also the knowledge of which MNP can be identified and how they differ along the length of the intestine. The studies included in this PhD reveal that both expected and newly identified subsets of MNP from blood can be identified in the human tissues. Furthermore, our data suggest that human MNP can develop in tissues from committed and possible uncommitted progenitors. We have also found that between the SI and colon the MNPs differ both in proportions and on gene level within the individual subsets, probably reflecting the environmental differences. We have further studied a subset of structural and supportive cells known as mesenchymal stromal cells (MSC). These were mostly uncharacterised at the beginning of this project and now our study adds to the understanding of their diversity, maintenance, locations and supportive functionality.
All of the above findings hep serve as a reference of the healthy intestine. This reference can help us learn how the MNPs and MSCs maintain and/or initiate inflammatory bowel disease and unveil possible new therapy targets.