期刊
IMMUNITY
卷 42, 期 5, 页码 953-964出版社
CELL PRESS
DOI: 10.1016/j.immuni.2015.04.016
关键词
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类别
资金
- Hormel Foundation
- Minnesota Obesity Center [5P30DK50456]
- Career Transition Fellowship (NMSS) [TA3047-A-1]
- NIH [CA18098601A1, CA17767901A1, CA157012]
- NIDDK [U24DK100469]
- NCATs [UL1TR000135]
Defining specific cellular and molecular mechanisms in most obesity-related diseases remains an important challenge. Here we report a serendipitous finding that consumption of a high-fat diet (HFD) greatly increased the occurrence of skin lesions in C57BL/6 mice. We demonstrated that HFD induced the accumulation of a specific type of CD11c(+) macrophages in skin preceding detectable lesions. These cells primed skin to induce IL-1 beta and IL-18 signaling, which further promoted the cytokines IFN-gamma-and IL-17-mediated skin inflammation. Mechanistically, epidermal fatty acid binding protein (E-FABP) was significantly upregulated in skin of obese mice, which coupled lipid droplet formation and NLRP3 inflammasome activation. Deficiency of E-FABP in obese mice decreased recruitment of CD11c(+) macrophages in skin tissues, reduced production of IL-1b and IL-18, and consequently dampened activation of effector T cells. Furthermore, E-FABP-deficient mice are completely resistant to HFD-induced skin lesions. Collectively, E-FABP represents a molecular sensor triggering HFD-induced skin inflammation.
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