Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR.

Animals Cellular Microenvironment / genetics Citric Acid Cycle / genetics Dendritic Cells / immunology Hexokinase / genetics Immunity, Innate Inflammation / genetics Mice Mice, Knockout Mitochondria / genetics Reactive Oxygen Species / immunology Toll-Like Receptors / genetics Unfolded Protein Response / genetics X-Box Binding Protein 1 / genetics
IL-23 UPR dendritic cells fatty acids glycolysis hexokinase innate immunity metabolic reprogramming mtROS psoriasis

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
16 05 2019
Historique:
received: 10 04 2018
revised: 27 01 2019
accepted: 08 03 2019
pubmed: 30 4 2019
medline: 12 2 2020
entrez: 30 4 2019
Statut: ppublish

Résumé

Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.

Identifiants

DOI: 10.1016/j.cell.2019.03.018 PMID: 31031005
pubmed: 31031005
pii: S0092-8674(19)30280-6
doi: 10.1016/j.cell.2019.03.018
pii:
doi:

Substances chimiques

Reactive Oxygen Species 0
Toll-Like Receptors 0
X-Box Binding Protein 1 0
Xbp1 protein, mouse 0
Hexokinase EC 2.7.1.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1201-1216.e19

Subventions

Organisme : Versus Arthritis
ID : 19867
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C29967/A26787
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C29967/A14633
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P010008/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M023230/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P010008/1
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Denis A Mogilenko (DA)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Joel T Haas (JT)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Laurent L'homme (L)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Sébastien Fleury (S)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Sandrine Quemener (S)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Matthieu Levavasseur (M)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France; Department of Dermatology, CHU Lille, 59045 Lille, France.

Coralie Becquart (C)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France; Department of Dermatology, CHU Lille, 59045 Lille, France.

Julien Wartelle (J)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Alexandra Bogomolova (A)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Laurent Pineau (L)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Olivier Molendi-Coste (O)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Steve Lancel (S)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Hélène Dehondt (H)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Celine Gheeraert (C)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Aurelie Melchior (A)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Cédric Dewas (C)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Artemii Nikitin (A)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Samuel Pic (S)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

Nabil Rabhi (N)

University of Lille, EGID, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199, 59019 Lille, France.

Jean-Sébastien Annicotte (JS)

University of Lille, EGID, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199, 59019 Lille, France.

Seiichi Oyadomari (S)

Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.

Talia Velasco-Hernandez (T)

Department of Hematology, Institute for Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden.

Jörg Cammenga (J)

Department of Hematology, Institute for Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden.

Marc Foretz (M)

Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France; INSERM U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France.

Benoit Viollet (B)

Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France; INSERM U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France.

Milica Vukovic (M)

Centre for Haemato-Oncology, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Arnaud Villacreces (A)

Centre for Haemato-Oncology, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Kamil Kranc (K)

Centre for Haemato-Oncology, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, 3000 Belgium.

Guillemette Marot (G)

Université Lille, MODAL Team, Inria Lille-Nord Europe, 59650 Villeneuve-d'Ascq, France.

Alexis Boulter (A)

University of Florida College of Medicine, Gainesville, FL 32610, USA.

Simon Tavernier (S)

Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research and Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium.

Luciana Berod (L)

Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.

Maria P Longhi (MP)

William Harvey Research Institute, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Christophe Paget (C)

Université de Tours, INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, 37041 Tours, France.

Sophie Janssens (S)

ER Stress and Inflammation, VIB Center for Inflammation Research, and Department of Internal Medicine and Pediatrics, Ghent University, 9052 Ghent, Belgium.

Delphine Staumont-Sallé (D)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France; Department of Dermatology, CHU Lille, 59045 Lille, France.

Ezra Aksoy (E)

Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.

Bart Staels (B)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France.

David Dombrowicz (D)

University of Lille, EGID, INSERM, CHU Lille, Institut Pasteur de Lille, U1011, 59019 Lille, France. Electronic address: david.dombrowicz@pasteur-lille.fr.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Cycle citrique › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Hexokinase › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Réponse aux protéines mal repliées › Metabolic and Innate Immune Cues Merge into a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Protéine-1 liant la boite X › Metabolic and Innate Immune Cues Merge into a...