Goblet cell-associated antigen passages in health and disease

In the gut, the immune system is exposed to self and dietary antigens and antigens from microbes including potential pathogens. How the immune system distinguishes between this wide array of substances to mount appropriate responses that range from tolerance to immunity is not well understood.

Accumulating evidence suggests that intestinal goblet cells may play a central role in the ability of the immune system to mount appropriate responses and to discriminate between innocuous substances and potential pathogens. Intestinal goblet cells can form goblet cell-associated antigen passages (GAPs), which acquire luminal substances and deliver them to the immune system. GAPs are closely regulated to not only control where and when antigen delivery to the immune system occurs but also to shape downstream immune outcomes. More recent studies suggest roles for GAPs in health and for GAP dysregulation as a contributor to disease.

Here, we review emerging studies and concepts on the role of goblet cells and GAPs, highlighting implications of these observations on the pathogenesis of, and potential therapies for, disease.