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, 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
Abstract
Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4+ T cells. Memory CD4+ T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4+ T cell differentiation into CD44hi-CCR7lo-CD62Llo-CXCR3+-LFA1+ effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4+ T cells and dendritic cells and was mediated via direct exposure of CD4+ T cells to palmitate, leading to increased activation of a PI3K p110δ-Akt-dependent pathway upon priming.
Keywords: Akt; CD4; T lymphocyte; differentiation; effector memory; high-fat diet; inflammation; obesity; palmitate; saturated fatty acid.
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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References
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