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  • Mogilenko, Denis A.Univ Lille, France (author)

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

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • CELL PRESS,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-158335
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-158335URI
  • https://doi.org/10.1016/j.cell.2019.03.018DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|ANR; European Union [EGID ANR-10-LABX-46, ANR-17-CE15-0030-02]; National Psoriasis Foundation (USA) Early Career Research Grant; EMBO Long-Term Fellowship; MRC [MR/M023230/1]; CRUK [C29967/A14633, C29967/A26787]; ERC advanced grant (ERC-2016-AdG) [694717]
  • 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 mitochondria! 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Haas, Joel T.Univ Lille, France (author)
  • Lhomme, LaurentUniv Lille, France (author)
  • Fleury, SebastienUniv Lille, France (author)
  • Quemener, SandrineUniv Lille, France (author)
  • Levavasseur, MatthieuUniv Lille, France; CHU Lille, France (author)
  • Becquart, CoralieUniv Lille, France; CHU Lille, France (author)
  • Wartelle, JulienUniv Lille, France (author)
  • Bogomolova, AlexandraUniv Lille, France (author)
  • Pineau, LaurentUniv Lille, France (author)
  • Molendi-Coste, OlivierUniv Lille, France (author)
  • Lancel, SteveUniv Lille, France (author)
  • Dehondt, HeleneUniv Lille, France (author)
  • Gheeraert, CelineUniv Lille, France (author)
  • Melchior, AurelieUniv Lille, France (author)
  • Dewas, CedricUniv Lille, France (author)
  • Nikitin, ArtemiiUniv Lille, France (author)
  • Pic, SamuelUniv Lille, France (author)
  • Rabhi, NabilUniv Lille, France (author)
  • Annicotte, Jean-SebastienUniv Lille, France (author)
  • Oyadomari, SeiichiTokushima Univ, Japan (author)
  • Velasco-Hernandez, TaliaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US(Swepub:liu)n/a (author)
  • Cammenga, JörgLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US(Swepub:liu)jorca02 (author)
  • Foretz, MarcUniv Paris 05, France; Inst Cochin, France; CNRS, France (author)
  • Viollet, BenoitUniv Paris 05, France; Inst Cochin, France; CNRS, France (author)
  • Vukovic, MilicaQueen Mary Univ London, England (author)
  • Villacreces, ArnaudQueen Mary Univ London, England (author)
  • Kranc, KamilQueen Mary Univ London, England (author)
  • Carmeliet, PeterVIB, Belgium; Univ Leuven, Belgium (author)
  • Marot, GuillemetteUniv Lille, France (author)
  • Boulter, AlexisUniv Florida, FL 32610 USA (author)
  • Tavernier, SimonUniv Ghent, Belgium; Univ Ghent, Belgium (author)
  • Berod, LucianaTWINCORE, Germany (author)
  • Longhi, Maria P.Queen Mary Univ London, England (author)
  • Paget, ChristopheUniv Tours, France (author)
  • Janssens, SophieUniv Ghent, Belgium (author)
  • Staumont-Salle, DelphineUniv Lille, France; CHU Lille, France (author)
  • Aksoy, EzraQueen Mary Univ London, England (author)
  • Staels, BartUniv Lille, France (author)
  • Dombrowicz, DavidUniv Lille, France (author)
  • Univ Lille, FranceUniv Lille, France; CHU Lille, France (creator_code:org_t)

Related titles

  • In:Cell: CELL PRESS177:5, s. 1201-0092-86741097-4172

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