Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4⁺ T Cell Differentiation via PI3K p110?-Akt-Mediated Signals.

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 CD44^hi-CCR7^lo-CD62L^lo-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 p110?-Akt-dependent pathway upon priming.

SUBMITTER: Mauro C 

PROVIDER: S-EPMC5355363 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature