Immune regulation of intestinal-stem-cell function in Drosophila

Intestinal progenitor cells integrate signals from their niche, and 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-microbe relationships, we know little about contributions of stem-cell immunity to gut homeostasis. We used Drosophila to determine the consequences of 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 found that inhibition of stem-cell immunity impeded progenitor-cell growth and differentiation, 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 stem cells for epithelial function in the adult gut. •The immune deficiency (IMD) pathway is active in Drosophila intestinal progenitors•Inhibition of IMD in progenitors impairs progenitor-cell proliferation•Blocking IMD in progenitors impairs generation of mature epithelial cells In this article, Foley and colleagues show that activation of IMD in intestinal progenitor cells regulates stem-cell proliferation and differentiation in the adult Drosophila midgut. Blocking progenitor-cell IMD impairs epithelial renewal and impacts the generation of mature enteroendocrine cells.