FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming

Nature Communications
Ivo S HansenJeroen den Dunnen

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.

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Citations

May 24, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Melissa NewlingJeroen den Dunnen
Sep 12, 2019·Clinical and Experimental Immunology·M NewlingJ den Dunnen
Apr 12, 2020·European Journal of Immunology·Rémi GayetStéphane Paul
Oct 23, 2019·Signal Transduction and Targeted Therapy·Ziying ZhangYongguang Tao
Dec 1, 2018·Cellular and Molecular Life Sciences : CMLS·Ivo S HansenJeroen den Dunnen
Apr 16, 2019·Frontiers in Immunology·Annelot Breedveld, Marjolein van Egmond
Dec 24, 2018·Frontiers in Immunology·Andrew J Stagg
Sep 25, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marlijn van der PoelJeroen den Dunnen
Nov 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Willianne HoepelJeroen den Dunnen
Feb 18, 2021·Journal for Immunotherapy of Cancer·Yan ZhangMingzhe Ma
Jan 16, 2021·ImmunoTargets and Therapy·Melissa Maria Johanna van Gool, Marjolein van Egmond
Jan 13, 2021·Nature Communications·Nicolas RochereauStéphane Paul
Oct 11, 2020·Signal Transduction and Targeted Therapy·Ziying ZhangYongguang Tao
May 13, 2021·Science Translational Medicine·Willianne HoepelJeroen den Dunnen
May 25, 2021·Journal of Immunological Methods·Ling LiuYi Yang
Jun 3, 2021·Cells·Chiara Elisabeth GeyerWillianne Hoepel
Aug 21, 2021·Cellular & Molecular Immunology·Sofie Hedlund MøllerPing-Chih Ho

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
density gradient centrifugation
ELISA
Assay

Software Mentioned

GraphPad Prism
GraphPad

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