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.

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals / C. Mauro, J. Smith, D. Cucchi, D. Coe, H. Fu, F. Bonacina, A. Baragetti, G. Cermenati, D. Caruso, N. Mitro, A.L. Catapano, E. Ammirati, M.P. Longhi, K. Okkenhaug, G.D. Norata, F.M. Marelli Berg. - In: CELL METABOLISM. - ISSN 1550-4131. - 25:3(2017 Mar), pp. 593-609. [10.1016/j.cmet.2017.01.008]

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals

F. Bonacina;A. Baragetti;G. Cermenati;D. Caruso;N. Mitro;A.L. Catapano;G.D. Norata
Penultimo
;
2017

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.
Akt; CD4; differentiation; effector memory; high-fat diet; inflammation; obesity; palmitate; saturated fatty acid; T lymphocyte; Physiology; Molecular Biology; Cell Biology
Settore BIO/14 - Farmacologia
Settore BIO/10 - Biochimica
mar-2017
http://www.cellmetabolism.org/
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/489842
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