Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
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 regu...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:19bdc7ef1aaa471e92f3cef5b5aedbdf2021-11-16T17:29:43ZIntestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis10.7554/eLife.672922050-084Xe67292https://doaj.org/article/19bdc7ef1aaa471e92f3cef5b5aedbdf2021-10-01T00:00:00Zhttps://elifesciences.org/articles/67292https://doaj.org/toc/2050-084XIntestinal 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.Jenny K GustafssonJazmyne E DavisTracy RappaiKeely G McDonaldDevesha H KulkarniKathryn A KnoopSimon P HoganJames AJ FitzpatrickWayne I LencerRodney D NewberryeLife Sciences Publications Ltdarticleintestinegoblet cellsantigen samplingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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intestine goblet cells antigen sampling Medicine R Science Q Biology (General) QH301-705.5 |
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intestine goblet cells antigen sampling Medicine R Science Q Biology (General) QH301-705.5 Jenny K Gustafsson Jazmyne E Davis Tracy Rappai Keely G McDonald Devesha H Kulkarni Kathryn A Knoop Simon P Hogan James AJ Fitzpatrick Wayne I Lencer Rodney D Newberry Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
description |
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. |
format |
article |
author |
Jenny K Gustafsson Jazmyne E Davis Tracy Rappai Keely G McDonald Devesha H Kulkarni Kathryn A Knoop Simon P Hogan James AJ Fitzpatrick Wayne I Lencer Rodney D Newberry |
author_facet |
Jenny K Gustafsson Jazmyne E Davis Tracy Rappai Keely G McDonald Devesha H Kulkarni Kathryn A Knoop Simon P Hogan James AJ Fitzpatrick Wayne I Lencer Rodney D Newberry |
author_sort |
Jenny K Gustafsson |
title |
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
title_short |
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
title_full |
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
title_fullStr |
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
title_full_unstemmed |
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
title_sort |
intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/19bdc7ef1aaa471e92f3cef5b5aedbdf |
work_keys_str_mv |
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