Metabolic control of regulatory T cell (Treg) survival and function by Lkb1

He Nanhai; Fan Weiwei; Henriquez BrianYu Ruth T.Atkins Annette R.Liddle ChristopherZheng YeDownes MichaelEvans Ronald M.

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Metabolic control of regulatory T cell (Treg) survival and function by Lkb1

机译：Metabolic control of regulatory T cell (Treg) survival and function by Lkb1

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The metabolic programs of functionally distinct T cell subsets are tailored to their immunologic activities. While quiescent T cells use oxidative phosphorylation (OXPHOS) for energy production, and effector T cells (Teffs) rely on glycolysis for proliferation, the distinct metabolic features of regulatory T cells (Tregs) are less well established. Here we show that the metabolic sensor LKB1 is critical to maintain cellular metabolism and energy homeostasis in Tregs. Treg-specific deletion of Lkb1 in mice causes loss of Treg number and function, leading to a fatal, early-onset autoimmune disorder. Tregs lacking Lkb1 have defective mitochondria, compromised OXPHOS, depleted cellular ATP, and altered cellular metabolism pathways that compromise their survival and function. Furthermore, we demonstrate that the function of LKB1 in Tregs is largely independent of the AMP-activated protein kinase, but is mediated by the MAP/microtubule affinity-regulating kinases and salt-inducible kinases. Our results define a metabolic checkpoint in Tregs that couples metabolic regulation to immune homeostasis and tolerance.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第47期|12542-12547|共6页
作者
He Nanhai; Fan Weiwei; Henriquez BrianYu Ruth T.Atkins Annette R.Liddle ChristopherZheng YeDownes MichaelEvans Ronald M.;
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作者单位

Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

Univ Sydney, Westmead Hosp, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW 2145, Australia;

Salk Inst Biol Studies, Nomis Labs Immunobiol & Microbial Pathogenesis, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Lkb1; Treg; Foxp3; cellular metabolism; autoimmune disease;

Metabolic control of regulatory T cell (Treg) survival and function by Lkb1

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