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首页> 外文期刊>Cell metabolism >Distinct iNKT Cell Populations Use IFN gamma or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis
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Distinct iNKT Cell Populations Use IFN gamma or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis

机译:明显的Inkt细胞群使用IFNγ或ER应激诱导的IL-10控制脂肪组织稳态

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摘要

Adipose tissue invariant natural killer T (iNKT) cells are phenotypically different from other iNKT cells because they produce IL-10 and control metabolic homeostasis. Why that is the case is unclear. Here, using single-cell RNA sequencing, we found several adipose iNKT clusters, which we grouped into two functional populations based on NK1.1 expression. NK1.1(NEG) cells almost exclusively produced IL-10 and other regulatory cytokines, while NK1.1(POS) iNKT cells predominantly produced IFN gamma. Mechanistically, biochemical fractionation revealed that free fatty acids drive IL-10 production primarily in NK1.1(NEG) iNKT cells via the IRE1 alpha-XBP1s arm of the unfolded protein response. Correspondingly, adoptive transfer of adipose tissue NK1.1(NEG) iNKT cells selectively restored metabolic function in obese mice. Further, we found an unexpected role for NK1.1(POS) iNKT cells in lean adipose tissue, as IFN gamma licenses natural killer cell-mediated macrophage killing to limit pathological macrophage expansion. Together, these two iNKT cell populations utilize non-redundant pathways to preserve metabolic integrity.
机译:脂肪组织不变自然杀伤T(Inkt)细胞与其他油墨细胞的表型不同,因为它们产生IL-10并控制代谢稳态。为什么案例尚不清楚。这里,使用单细胞RNA测序,我们发现了几种脂肪油墨簇,我们将其分组为基于NK1.1表达的两种功能群体。 NK1.1(Neg)细胞几乎完全产生IL-10和其他调节细胞因子,而NK1.1(POS)Inkt细胞主要产生IFNγ。机械地,生化分级显示,游离脂肪酸主要通过展开蛋白质反应的IS1α-XBP1S臂在NK1.1(NON)Inkt细胞中驱动IL-10产生。相应地,脂肪组织NK1.1(NEG)Inkt细胞的养老组织NK1.1(Neg)Inkt细胞在肥胖小鼠中选择性地恢复代谢功能。此外,我们发现瘦脂肪组织中的NK1.1(POS)Inkt细胞的意外作用,如IFNγ许可的天然杀手细胞介导的巨噬细胞杀伤以限制病理巨噬细胞扩张。在一起,这两个Inkt细胞群利用非冗余途径来保持代谢完整性。

著录项

  • 来源
    《Cell metabolism》 |2020年第2期|共22页
  • 作者单位

    Brigham &

    Womens Hosp Div Rheumatol Inflammat &

    Immun 75 Francis St Boston MA 02115 USA;

    Trinity Coll Dublin Trinity Biomed Sci Inst Dublin Ireland;

    Brigham &

    Womens Hosp Div Genet 75 Francis St Boston MA 02115 USA;

    Dana Farber Canc Inst Dept Canc Immunol &

    Virol Boston MA 02115 USA;

    Trinity Coll Dublin Trinity Biomed Sci Inst Dublin Ireland;

    Brigham &

    Womens Hosp Div Rheumatol Inflammat &

    Immun 75 Francis St Boston MA 02115 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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