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 to maintain 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 impacted 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 an impaired differentiation of mature enteroendocrine cells. Our results highlight the importance of immune signaling in the stem cell population for epithelial function in the adult gut. HIGHLIGHTS The TNFR-like Immune Deficiency (IMD) pathway is active in Drosophila intestinal progenitor cells. Inhibition of IMD in progenitors impairs progenitor cell proliferation. Blocking progenitor cell IMD negatively affects generation of mature epithelial cells.