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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...

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Autores principales: 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
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
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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.
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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
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