Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals
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Colleges, School and Institutes
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.
|Number of pages||18|
|Early online date||9 Feb 2017|
|Publication status||Published - 1 Mar 2017|
- CD4, T lymphocyte, effector memory, differentiation, obesity, high-fat diet, inflammation, palmitate, saturated fatty acid, Akt