期刊
CELL METABOLISM
卷 25, 期 3, 页码 593-609出版社
CELL PRESS
DOI: 10.1016/j.cmet.2017.01.008
关键词
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资金
- British Heart Foundation [FS/12/38/29640, PG/15/105/31906]
- Fondazione Cariplo [2015-0552]
- National Institutes of Health Research
- Istituto Pasteur, Fondazione Cenci-Bolognetti
- Telethon Foundation [GGP13002]
- Italian Ministero della Salute [WFR GR-2011-02346974]
- British Heart Foundation Chair of Cardiovascular Immunology [CH/15/2/32064]
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0407, BBS/E/B/000C0409, BBS/E/B/000C0428, BBS/E/B/000C0427] Funding Source: researchfish
- British Heart Foundation [FS/11/64/28945, RG/14/2/30616, FS/12/38/29640, FS/13/49/30421, PG/15/105/31906] Funding Source: researchfish
- Medical Research Council [1263270] Funding Source: researchfish
- BBSRC [BBS/E/B/000C0407, BBS/E/B/000C0409, BBS/E/B/000C0427, BBS/E/B/000C0428] Funding Source: UKRI
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 highfat 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 delta-Akt-dependent pathway upon priming.
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