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 language | English |
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Pages (from-to) | 593-609 |
Number of pages | 18 |
Journal | Cell Metabolism |
Volume | 25 |
Issue number | 3 |
Early online date | 9 Feb 2017 |
DOIs | |
Publication status | Published - 1 Mar 2017 |
Keywords
- CD4
- T lymphocyte
- effector memory
- differentiation
- obesity
- high-fat diet
- inflammation
- palmitate
- saturated fatty acid
- Akt