Skip to Main content Skip to Navigation
Journal articles

Metabolic and innate immune cues merge into a specific inflammatory response via unfolded protein response (UPR)

Denis A Mogilenko 1 Joël Haas 1 Laurent L'Homme 1 Sébastien Fleury 1 Sandrine Quemener 1 Matthieu Levavasseur 1, 2 Coralie Becquart 1, 2 Julien Wartelle 1 Alexandra Bogomolova 1 Laurent Pineau 1 Olivier Molendi-Coste 1 Steve Lancel 1 Hélène Dehondt 1 Céline Gheeraert 1 Aurélie Melchior 1 Cédric Dewas 1 Artemii Nikitin 1 Samuel Pic 1 Nabil Rabhi 3 Jean-Sébastien Annicotte 3 Seiichi Oyadomari 4 Talia Velasco-Hernandez 5 Jörg Cammenga 5 Marc Foretz 6, 7 Benoit Viollet 6, 7 Milica Vukovic 8 Arnaud Villacreces 8 Kamil Kranc 8 Peter Carmeliet 9, 10 Guillemette Marot 11 Alexis Boulter 12 Simon J. Tavernier 13 Luciana Berod 14 Maria P. Longhi 15 Christophe Paget 16 Sophie Janssens 17 Delphine Staumont-Sallé 1, 18 Ezra Aksoy 19 Bart Staels 1 David Dombrowicz 1, * 
* Corresponding author
11 MODAL - MOdel for Data Analysis and Learning
LPP - Laboratoire Paul Painlevé - UMR 8524, Université de Lille, Sciences et Technologies, Inria Lille - Nord Europe, METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Polytech Lille - École polytechnique universitaire de Lille
Abstract : 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 (DC) are exacerbated by a high fatty acid (FA) metabolic environment. FA 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.
Complete list of metadata

Cited literature [4 references]  Display  Hide  Download
Contributor : Christine Dupuis Connect in order to contact the contributor
Submitted on : Friday, March 29, 2019 - 3:45:07 PM
Last modification on : Friday, July 8, 2022 - 10:05:33 AM
Long-term archiving on: : Sunday, June 30, 2019 - 4:36:12 PM



Denis A Mogilenko, Joël Haas, Laurent L'Homme, Sébastien Fleury, Sandrine Quemener, et al.. Metabolic and innate immune cues merge into a specific inflammatory response via unfolded protein response (UPR). Cell, Elsevier, In press, 177 (5), pp.1201-1216.e19. ⟨10.1016/j.cell.2019.03.018⟩. ⟨inserm-02084447⟩



Record views


Files downloads