Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis

eLife

Tracy Rappai¹  James AJ Fitzpatrick²  Jazmyne E Davis³  Devesha H Kulkarni³  Keely G McDonald³  Kathryn A Knoop³  Rodney D Newberry³  Jenny K Gustafsson⁴  Wayne I Lencer⁵  Simon P Hogan⁶ 

[1] Center for Cellular Imaging, Washington University School of Medicine, St Louis, United States;Center for Cellular Imaging, Washington University School of Medicine, St Louis, United States;Department of Cell Biology &Physiology, Washington University School of Medicine, St Louis, United States;Department of Neuroscience, Washington University School of Medicine, St Louis, United States;Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, United States;Department of Internal Medicine, Washington University School of Medicine, St Louis, United States;Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Department of Internal Medicine, Washington University School of Medicine, St Louis, United States;Department of Pediatrics, Harvard Medical School, Boston, United States;Division of Gastroenterology, Nutrition and Hepatology, Boston Children’s Hospital, Boston, United States;Harvard Digestive Disease Center, Harvard Medical School, Boston, United States;Mary H. Weiser Food Allergy Center, University of Michigan School of Medicine,, Ann Arbor, United States;

关键词: intestine;    goblet cells;    antigen sampling;    Mouse;   

DOI  :  10.7554/eLife.67292

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis – in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and lysosomes. While ACh also induced goblet cells to secrete mucins, ACh-induced GAP formation and mucin secretion were functionally independent and mediated by different receptors and signaling pathways, enabling goblet cells to differentially regulate these processes to accommodate the dynamically changing demands of the mucosal environment for barrier maintenance and sampling of lumenal substances.

【 授权许可】

CC BY