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

Research output: Contribution to journalArticle

Authors

  • 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

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)593-609
Number of pages18
JournalCell Metabolism
Volume25
Issue number3
Early online date9 Feb 2017
Publication statusPublished - 1 Mar 2017

Keywords

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