Cargando…
FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming
CD103(+) dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after ba...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830413/ https://www.ncbi.nlm.nih.gov/pubmed/29491406 http://dx.doi.org/10.1038/s41467-018-03318-5 |
_version_ | 1783302992838000640 |
---|---|
author | Hansen, Ivo S. Krabbendam, Lisette Bernink, Jochem H. Loayza-Puch, Fabricio Hoepel, Willianne van Burgsteden, Johan A. Kuijper, Elsa C. Buskens, Christianne J. Bemelman, Willem A. Zaat, Sebastiaan A. J. Agami, Reuven Vidarsson, Gestur van den Brink, Gijs R. de Jong, Esther C. Wildenberg, Manon E. Baeten, Dominique L. P. Everts, Bart den Dunnen, Jeroen |
author_facet | Hansen, Ivo S. Krabbendam, Lisette Bernink, Jochem H. Loayza-Puch, Fabricio Hoepel, Willianne van Burgsteden, Johan A. Kuijper, Elsa C. Buskens, Christianne J. Bemelman, Willem A. Zaat, Sebastiaan A. J. Agami, Reuven Vidarsson, Gestur van den Brink, Gijs R. de Jong, Esther C. Wildenberg, Manon E. Baeten, Dominique L. P. Everts, Bart den Dunnen, Jeroen |
author_sort | Hansen, Ivo S. |
collection | PubMed |
description | CD103(+) dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103(+)SIRPα(+) DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103(+) DCs. These cells then enhance inflammation by promoting Th17 responses and activating human intestinal innate lymphoid cells 3. Moreover, FcαRI-induced cytokine production is orchestrated via upregulation of cytokine translation and caspase-1 activation, which is dependent on glycolytic reprogramming mediated by kinases Syk, PI3K and TBK1-IKKε. Our data suggest that the formation of IgA-IC in the human intestine provides an environmental cue for the conversion of a tolerogenic to an inflammatory response. |
format | Online Article Text |
id | pubmed-5830413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58304132018-03-05 FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming Hansen, Ivo S. Krabbendam, Lisette Bernink, Jochem H. Loayza-Puch, Fabricio Hoepel, Willianne van Burgsteden, Johan A. Kuijper, Elsa C. Buskens, Christianne J. Bemelman, Willem A. Zaat, Sebastiaan A. J. Agami, Reuven Vidarsson, Gestur van den Brink, Gijs R. de Jong, Esther C. Wildenberg, Manon E. Baeten, Dominique L. P. Everts, Bart den Dunnen, Jeroen Nat Commun Article CD103(+) dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103(+)SIRPα(+) DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103(+) DCs. These cells then enhance inflammation by promoting Th17 responses and activating human intestinal innate lymphoid cells 3. Moreover, FcαRI-induced cytokine production is orchestrated via upregulation of cytokine translation and caspase-1 activation, which is dependent on glycolytic reprogramming mediated by kinases Syk, PI3K and TBK1-IKKε. Our data suggest that the formation of IgA-IC in the human intestine provides an environmental cue for the conversion of a tolerogenic to an inflammatory response. Nature Publishing Group UK 2018-02-28 /pmc/articles/PMC5830413/ /pubmed/29491406 http://dx.doi.org/10.1038/s41467-018-03318-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hansen, Ivo S. Krabbendam, Lisette Bernink, Jochem H. Loayza-Puch, Fabricio Hoepel, Willianne van Burgsteden, Johan A. Kuijper, Elsa C. Buskens, Christianne J. Bemelman, Willem A. Zaat, Sebastiaan A. J. Agami, Reuven Vidarsson, Gestur van den Brink, Gijs R. de Jong, Esther C. Wildenberg, Manon E. Baeten, Dominique L. P. Everts, Bart den Dunnen, Jeroen FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title | FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title_full | FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title_fullStr | FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title_full_unstemmed | FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title_short | FcαRI co-stimulation converts human intestinal CD103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
title_sort | fcαri co-stimulation converts human intestinal cd103(+) dendritic cells into pro-inflammatory cells through glycolytic reprogramming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830413/ https://www.ncbi.nlm.nih.gov/pubmed/29491406 http://dx.doi.org/10.1038/s41467-018-03318-5 |
work_keys_str_mv | AT hansenivos fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT krabbendamlisette fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT berninkjochemh fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT loayzapuchfabricio fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT hoepelwillianne fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT vanburgstedenjohana fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT kuijperelsac fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT buskenschristiannej fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT bemelmanwillema fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT zaatsebastiaanaj fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT agamireuven fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT vidarssongestur fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT vandenbrinkgijsr fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT dejongestherc fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT wildenbergmanone fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT baetendominiquelp fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT evertsbart fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming AT dendunnenjeroen fcaricostimulationconvertshumanintestinalcd103dendriticcellsintoproinflammatorycellsthroughglycolyticreprogramming |