Lipid antigens in adipose tissue : A CD1d centered view on adipocyte - iNKT cell communication

Abstract

Fat tissue is more than just fat cells that store lipids. It is a highly complex tissue with a large variety of different cells that have different functions both locally and throughout the whole body. Fat cells for example, communicate with their surroundings by secreting specific signaling molecules (indirect) or through direct interaction with mainly immune cells. This communication is key for fat tissue to remain healthy. One immune cell in particular seems to play an important role in maintaining a healthy environment: invariant Natural Killer T (iNKT) cells. These cells interact with fat cells through one specific protein, named CD1d, expressed on the outer surface of fat cells. CD1d is a protein that presents lipid antigens to the iNKT cells resulting in activation of iNKT cells. This thesis dives in to the details of this interaction. What kind of self made lipid antigens are presented by CD1d? And how can they regulate iNKT cell activaty? And finally, How do metabolic changes like obesity affect iNKT cell biology in fat tissue? These are very big questions, and this thesis provides a starting point for all three questions to be answered. We found that in a high lipid environment, iNKT cells behave more pro-inflammatory. Also, we showed the presence of a pathway that produces potential lipid antigens in fat cells that is involved in iNKT cell activation through CD1d. Finally, we created a method to highly specific isolate CD1d from fat cells to study the nature of the lipid antigen it presents.