#IDIBELLseminars: Defining epithelial changes in early-life gut development and immunity to infection

Menno Oudhoof
Centre for Molecular Inflammation Research (CEMIR)

Epithelium is fundamental for our health and wellbeing. Its barrier role is essential for many organs. Additionally, tissue-specific aspects, such as nutrient uptake by specialized intestinal epithelium, are important for our daily functioning. Of course, the epithelium does not act alone. Tissue protection is orchestrated by many factors including the interplay between epithelium, associated microbiota and tissue-resident immune cells. The gut is an exceptional example: it has a single layer of epithelial cells that is structured to maximize its surface area to ~250 m2, it hosts 1014 commensal bacteria, and has immune cells that mediate tolerance. This delicate balance and barrier function is set up early in life where significant changes in microbiota, epithelium, and immune cell composition occur. We study how early life epithelium is established, and how intrinsic epigenetic regulation is controlling the early life epithelial transition. We also study how, later in life, in response to infection or inflammation, the epithelium undergoes reversible changes that are mediated by immune-cell secreted cytokines. We propose that during infection, mediated by cytokines, the epithelium undergoes similar changes as compared to the early life transition and cytokine signaling is intertwining with developmental pathways to ultimately provide immunity to infection. In our work, we combine in vivo mouse models with in vitro organoid work to both study cellular and molecular mechanisms. In this presentation, I will provide an overview of our recent and current work.

Hosted by Jordi Guiu

Menno received his PhD in biochemistry from the VU University in Amsterdam, The Netherlands, in December 2006. During his PhD, he studied human saliva and how salivary peptides help oral wound healing. This work included the discovery of histatin as the major active component to stimulate epithelial migration, and the finding that cyclization of the normally linear histatin potentiates its activity ~1,000 fold. In early 2010, he moved to UBC in Vancouver, Canada, to join the lab of Colby Zaph in mucosal immunology. Here, he worked on the role of the lysine methyltransferase SETD7 in its role in intestinal regeneration, tumorigenesis, and immunity. In the spring of 2016, he started his own group at CEMIR in Trondheim, Norway. His lab studies intestinal epithelial regeneration, a process that is linked to development, inflammation, infection, and tumorigenesis. His work specifically focuses on how reparative programs are controlled intrinsically by epigenetic modifiers, and by cues from other cells such as niche factors from mesenchymal cells and cytokines from immune cells.