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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: Gustafsson, Jenny K, Davis, Jazmyne E, Rappai, Tracy, McDonald, Keely G, Kulkarni, Devesha H, Knoop, Kathryn A, Hogan, Simon P, Fitzpatrick, James AJ, Lencer, Wayne I, Newberry, Rodney D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594945/
https://www.ncbi.nlm.nih.gov/pubmed/34677124
http://dx.doi.org/10.7554/eLife.67292
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author Gustafsson, Jenny K
Davis, Jazmyne E
Rappai, Tracy
McDonald, Keely G
Kulkarni, Devesha H
Knoop, Kathryn A
Hogan, Simon P
Fitzpatrick, James AJ
Lencer, Wayne I
Newberry, Rodney D
author_facet Gustafsson, Jenny K
Davis, Jazmyne E
Rappai, Tracy
McDonald, Keely G
Kulkarni, Devesha H
Knoop, Kathryn A
Hogan, Simon P
Fitzpatrick, James AJ
Lencer, Wayne I
Newberry, Rodney D
author_sort Gustafsson, Jenny K
collection PubMed
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.
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spelling pubmed-85949452021-11-17 Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis Gustafsson, Jenny K Davis, Jazmyne E Rappai, Tracy McDonald, Keely G Kulkarni, Devesha H Knoop, Kathryn A Hogan, Simon P Fitzpatrick, James AJ Lencer, Wayne I Newberry, Rodney D eLife Cell Biology 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. eLife Sciences Publications, Ltd 2021-10-22 /pmc/articles/PMC8594945/ /pubmed/34677124 http://dx.doi.org/10.7554/eLife.67292 Text en © 2021, Gustafsson et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Gustafsson, Jenny K
Davis, Jazmyne E
Rappai, Tracy
McDonald, Keely G
Kulkarni, Devesha H
Knoop, Kathryn A
Hogan, Simon P
Fitzpatrick, James AJ
Lencer, Wayne I
Newberry, Rodney D
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
title 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_short 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
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594945/
https://www.ncbi.nlm.nih.gov/pubmed/34677124
http://dx.doi.org/10.7554/eLife.67292
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