Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
- University of Gothenburg, Sweden
- Washington University in Saint Louis School of Medicine, United States
- University of Michigan, United States
- Washington University School of Medicine, United States
- Harvard Medical School, United States
Abstract
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.
Data availability
All data generated and analysed for this study are included in the manuscript and source data files for figure 8
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK097317)
- Rodney D Newberry
Stiftelserna Wilhelm och Martina Lundgrens
- Jenny K Gustafsson
Åke Wiberg Stiftelse
- Jenny K Gustafsson
Jeanssons Stiftelser
- Jenny K Gustafsson
National Institute of Allergy and Infectious Diseases (AI131342)
- Rodney D Newberry
National Institute of Diabetes and Digestive and Kidney Diseases (DK109006)
- Kathryn A Knoop
National Institute of Allergy and Infectious Diseases (AI136515)
- Rodney D Newberry
National Institute of Allergy and Infectious Diseases (AI140755)
- Rodney D Newberry
National Institute of Allergy and Infectious Diseases (AI112626)
- Simon P Hogan
National Institute of Diabetes and Digestive and Kidney Diseases (DK048106)
- Wayne I Lencer
Crohn's and Colitis Foundation (34835)
- Jenny K Gustafsson
Vetenskapsrådet (2014-00366)
- Jenny K Gustafsson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures and protocols were performed in accordance with the Institutional Animal Care and Use Committee at Washington University School of Medicine (Animal Wellfare Assurance number: A-3381-01) and the Swedish animal welfare legislation and approved by the Swedish Laboratory Animal Ethical Committee in Gothenburg (Ethical permit ID number: 5.8.18-11053/2019.
Copyright
© 2021, Gustafsson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
eLife 10:e67292.
https://doi.org/10.7554/eLife.67292
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