美国布莱根妇女医院Michael B. Brenner研究组近日取得一项新成果。他们的最新研究揭示不同的不变性自然杀伤T细胞（iNKT）细胞群体利用IFNγ或内质网（ER）应激诱导的IL-10来控制脂肪组织稳态。相关论文于2020年6月8日发表于《细胞-代谢》。

使用单细胞RNA测序，他们发现了几个脂肪iNKT簇，他们根据NK1.1表达将它们分为两个功能群。NK1.1NEG细胞几乎只产生IL-10和其他调节性细胞因子，而NK1.1POS iNKT细胞则主要产生IFNγ。从机理上讲，生化分级显示，游离脂肪酸主要通过未折叠蛋白应答的IRE1α-XBP1s臂，驱动NK1.1NEG iNKT细胞中IL-10的产生。相应地，脂肪组织NK1.1NEG iNKT细胞的过继转移选择性地恢复了肥胖小鼠的代谢功能。

此外，他们发现瘦肉脂肪组织中NK1.1POS iNKT细胞具有意想不到的作用，因为IFNγ许可自然杀伤细胞介导的巨噬细胞杀伤作用，从而限制了病理性巨噬细胞的扩增。这两个iNKT细胞群体一起利用非冗余途径来保持代谢完整性。

据了解，脂肪组织iNKT与其他iNKT细胞在表型上有所不同，因为它们产生IL-10并控制代谢稳态。目前尚不清楚其中的原因。

附：英文原文

Title: Distinct iNKT Cell Populations Use IFNγ or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis

Author: Nelson M. LaMarche, Harry Kane, Ayano C. Kohlgruber, Han Dong, Lydia Lynch, Michael B. Brenner

Issue&Volume: 2020-06-08

Abstract: Adipose tissue invariant natural killer T (iNKT) cells are phenotypically differentfrom 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 foundseveral adipose iNKT clusters, which we grouped into two functional populations basedon NK1.1 expression. NK1.1NEG cells almost exclusively produced IL-10 and other regulatory cytokines, while NK1.1POS iNKT cells predominantly produced IFNγ. Mechanistically, biochemical fractionationrevealed that free fatty acids drive IL-10 production primarily in NK1.1NEG iNKT cells via the IRE1α-XBP1s arm of the unfolded protein response. Correspondingly,adoptive transfer of adipose tissue NK1.1NEG iNKT cells selectively restored metabolic function in obese mice. Further, we foundan unexpected role for NK1.1POS iNKT cells in lean adipose tissue, as IFNγ licenses natural killer cell-mediatedmacrophage killing to limit pathological macrophage expansion. Together, these twoiNKT cell populations utilize non-redundant pathways to preserve metabolic integrity.

DOI: 10.1016/j.cmet.2020.05.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30256-4