Abstract：
:The function of regulatory T (Treg) cells depends on lipid oxidation. However, the molecular mechanism by which Treg cells maintain lipid metabolism after activation remains elusive. Liver kinase B1 (LKB1) acts as a coordinator by linking cellular metabolism to substrate AMP-activated protein kinase (AMPK). We show that deletion of LKB1 in Treg cells exhibited reduced suppressive activity and developed fatal autoimmune inflammation. Mechanistically, LKB1 induced activation of the mevalonate pathway by upregulating mevalonate genes, which was essential for Treg cell functional competency and stability by inducing Treg cell proliferation and suppressing interferon-gamma and interleukin-17A expression independently of AMPK. Furthermore, LKB1 was found to regulate intracellular cholesterol homeostasis and to promote the mevalonate pathway. In agreement, mevalonate and its metabolite geranylgeranyl pyrophosphate inhibited conversion of Treg cells and enhanced survival of LKB1-deficient Treg mice. Thus, LKB1 is a key regulator of lipid metabolism in Treg cells, involved in optimal programming of suppressive activity, immune homeostasis, and tolerance.
journal_name
Cell Repjournal_title
Cell reportsauthors
Timilshina M,You Z,Lacher SM,Acharya S,Jiang L,Kang Y,Kim JA,Chang HW,Kim KJ,Park B,Song JH,Ko HJ,Park YY,Ma MJ,Nepal MR,Jeong TC,Chung Y,Waisman A,Chang JHdoi
10.1016/j.celrep.2019.05.020subject
Has Abstractpub_date
2019-06-04 00:00:00pages
2948-2961.e7issue
10issn
2211-1247pii
S2211-1247(19)30631-Xjournal_volume
27pub_type
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