德国马克斯·普朗克免疫生物学和表观遗传学研究所Erika L. Pearce团队发现，脂质代谢调节的线粒体完整性是调节性T细胞（Tregs）抑制功能的细胞内在检查点。该研究2019年12月26日在线发表在国际学术期刊《细胞—代谢》杂志上。

研究人员发现在Tregs中，利用遗传或药物抑制FABP5的功能会导致线粒体改变，造成这种改变的原因是OXPHOS降低、脂质代谢受损以及嵴结构的丢失。在Tregs中抑制FABP5会导致mtDNA释放，从而引起cGAS-STING依赖性I型IFN信号传导，这会增加调节性细胞因子IL-10的产生并促进Treg抑制活性。

研究人员发现了支撑该途径的证据以及相关线粒体肿瘤浸润Tregs的变化，这可能是造成肿瘤微环境中免疫抑制作用增强的基础。总之，这项研究证明FABP5是线粒体完整性的守护者并调节Treg的功能。

据了解，Tregs抑制免疫反应。对Treg激活起关键作用的是脂代谢的变化，这些变化维持了其生存和功能。脂肪酸结合蛋白（FABPs）是细胞内促进脂肪摄取和运输所需的脂伴侣家族。该家族成员FABP5在T细胞中表达，但尚不清楚其功能。

附：英文原文

Title: Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function

Author: Cameron S. Field, Francesc Baixauli, Ryan L. Kyle, Daniel J. Puleston, Alanna M. Cameron, David E. Sanin, Keli L. Hippen, Michael Loschi, Govindarajan Thangavelu, Mauro Corrado, Joy Edwards-Hicks, Katarzyna M. Grzes, Edward J. Pearce, Bruce R. Blazar, Erika L. Pearce

Issue&Volume: December 26, 2019

Abstract: Regulatory T cells (Tregs) subdue immune responses. Central to Treg activation are changes in lipid metabolism that support their survival and function. Fatty acid binding proteins (FABPs) are a family of lipid chaperones required to facilitate uptake and intracellular lipid trafficking. One family member, FABP5, is expressed in T cells, but its function remains unclear. We show that in Tregs, genetic or pharmacologic inhibition of FABP5 function causes mitochondrial changes underscored by decreased OXPHOS, impaired lipid metabolism, and loss of cristae structure. FABP5 inhibition in Tregs triggers mtDNA release and consequent cGAS-STING-dependent type I IFN signaling, which induces heightened production of the regulatory cytokine IL-10 and promotes Treg suppressive activity. We find evidence of this pathway, along with correlative mitochondrial changes in tumor infiltrating Tregs, which may underlie enhanced immunosuppression in the tumor microenvironment. Together, our data reveal that FABP5 is a gatekeeper of mitochondrial integrity that modulates Treg function.

DOI: 10.1016/j.cmet.2019.11.021

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30665-5