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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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/19bdc7ef1aaa471e92f3cef5b5aedbdf
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic intestine
goblet cells
antigen sampling
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle 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
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