Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals

Claudio Mauro, Joanne Smith, Danilo Cucchi, David Coe, Hongmei Fu, Fabrizia Bonacina, Andrea Baragetti, Gaia Cermenati, Donatella Caruso, Nico Mitro, Alberico L. Catapano, Enrico Ammirati, Maria P. Longhi, Klaus Okkenhaug, Giuseppe D. Norata, Federica M. Marelli-berg

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)
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Abstract

Low-grade systemic inflammation associated toobesity leads to cardiovascular complications,caused partly by infiltration of adipose and vasculartissue by effector T cells. The signals leading toT cell differentiation and tissue infiltration duringobesity are poorly understood. We tested whethersaturated fatty acid-induced metabolic stress affectsdifferentiation and trafficking patterns of CD4+T cells.Memory CD4+T cells primed in high-fat diet-fed do-nors preferentially migrated to non-lymphoid, inflam-matory sites, independent of the metabolic status ofthe hosts. This was due to biased CD4+T cell differen-tiation into CD44hi-CCR7lo-CD62Llo-CXCR3+-LFA1+effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observedin obese subjects in a cohort of free-living people. Thisdevelopmental bias was independent of any cross-talk between CD4+T cells and dendritic cells andwas mediated via direct exposure of CD4+T cells topalmitate, leading to increased activation of a PI3Kp110δ-Akt-dependent pathway upon priming.
Original languageEnglish
Pages (from-to)593-609
Number of pages18
JournalCell Metabolism
Volume25
Issue number3
Early online date9 Feb 2017
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • CD4
  • T lymphocyte
  • effector memory
  • differentiation
  • obesity
  • high-fat diet
  • inflammation
  • palmitate
  • saturated fatty acid
  • Akt

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