Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4<sup>+</sup> T Cell Differentiation via PI3K p110d-Akt-Mediated Signals
|dc.identifier.citation||Mauro, C. and Smith, J. and Cucchi, D. and Coe, D. and Fu, H. and Bonacina, F. and Baragetti, A. et al. 2017. Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4<sup>+</sup> T Cell Differentiation via PI3K p110d-Akt-Mediated Signals. Cell Metabolism. 25 (3): pp. 593-609.|
© 2017 The Author(s) 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 p110d-Akt-dependent pathway upon priming.
|dc.title||Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4<sup>+</sup> T Cell Differentiation via PI3K p110d-Akt-Mediated Signals|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Open access via publisher|
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