Department of Medical Microbiology and Immunology Faculty of Medicine and Dentistry University of Alberta Edmonton, Edmonton, AB Canada.
Department of Medical Microbiology and Immunology Faculty of Medicine and Dentistry University of Alberta Edmonton, Edmonton, AB Canada; Department of Cell Biology Faculty of Medicine and Dentistry University of Alberta Edmonton, Edmonton AB, Canada.
Stem Cell Reports. 2022 Apr 12;17(4):741-755. doi: 10.1016/j.stemcr.2022.02.009. Epub 2022 Mar 17.
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.
肠祖细胞整合其龛位和肠道腔的信号，以一定的速度分裂和分化，从而维持上皮屏障，防止微生物入侵宿主内部。尽管进化上保守的先天免疫防御对于维持稳定的宿主-微生物关系至关重要，但我们对干细胞免疫对肠道稳态的贡献知之甚少。我们使用果蝇来确定肠干细胞免疫活性对上皮稳态的影响。我们发现，丧失干细胞免疫会极大地影响成年肠道的生长和更新。具体来说，我们发现抑制干细胞免疫会阻碍祖细胞的生长和分化，导致随着年龄的增长干细胞数量逐渐减少，以及成熟肠内分泌细胞的分化受损。我们的研究结果强调了免疫信号在成年肠道中干细胞上皮功能中的重要性。
