Immune Regulation of Intestinal Stem Cell Proliferation and Differentiation in Drosophila

ABSTRACT Intestinal progenitor cells integrate signals from their niche, and from the gut lumen, to divide and differentiate at a rate that maintains an epithelial barrier to microbial invasion of the host interior. Despite the importance of evolutionarily-conserved innate immune defenses for the maintenance of stable host-microbiota relationships, we know little about specific contributions of stem cell immunity to gut homeostasis. We used the Drosophila model to determine the consequences of compromised intestinal stem cell immune activity for epithelial homeostasis. We showed that loss of stem cell immunity greatly impacts growth and renewal in the adult gut. In particular, we noticed that inhibition of stem cell immunity impeded key growth and differentiation events in the progenitor cell compartment leading to a gradual loss of stem cell numbers with age, and impaired differentiation of mature enteroendocrine cells. Our results emphasize the importance of immune signaling in the stem cell population for epithelial function in the adult gut.