Abstract

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.

Details

Title
FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming
Author
Hansen, Ivo S 1 ; Krabbendam, Lisette 2 ; Bernink, Jochem H 2 ; Loayza-Puch, Fabricio 3   VIAFID ORCID Logo  ; Hoepel, Willianne 1 ; van Burgsteden, Johan A 1 ; Kuijper, Elsa C 4 ; Buskens, Christianne J 5 ; Bemelman, Willem A 5 ; Zaat, Sebastiaan A J 6 ; Agami, Reuven 3 ; Vidarsson, Gestur 7   VIAFID ORCID Logo  ; Gijs R van den Brink 8 ; de Jong, Esther C 2 ; Wildenberg, Manon E 8 ; Baeten, Dominique L P 1 ; Everts, Bart 4 ; den Dunnen, Jeroen 1 

1  Amsterdam Rheumatology and Immunology Centre, Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
2  Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
3  Division of Oncogenomics, Netherlands Cancer Institute, Amsterdam, The Netherlands 
4  Department of Parasitology, Leiden University Medical Centre, University of Leiden, Leiden, The Netherlands 
5  Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
6  Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
7  Department of Experimental Immunohematology, Sanquin Research, University of Amsterdam, Amsterdam, The Netherlands 
8  Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
Pages
1-13
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03318-5
ProQuest document ID
2009220622
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.