LKB1 expressed in dendritic cells governs the development and expansion of thymus-derived regulatory T cells  

作　　者：Leonard R.Pelgrom Thiago A.Patente Alexey Sergushichev Ekaterina Esaulova Frank Otto Arifa Ozir-Fazalalikhan Hendrik J.P.van der Zande Alwin J.van der Ham Stefan van der Stel Maxim N.Artyomov Bart Everts 

机构地区：[1]Department of Parasitology,Leiden University Medical Center,Leiden,The Netherlands [2]Computer Technologies Department,ITMO University,Saint Petersburg,Russia [3]Department of Pathology and Immunology,Washington University School of Medicine,St.Louis,USA

出　　处：《Cell Research》2019年第5期406-419,共14页细胞研究（英文版）

摘　　要：Liver Kinase B1(LKB1)plays a key role in cellular metabolism by controlling AMPK activation.However,its function in dendritic cell(DC)biology has not been addressed.Here,we find that LKB1 functions as a critical brake on DC immunogenicity,and when lost,leads to reduced mitochondrial fitness and increased maturation,migration,and T cell priming of peripheral DCs.Concurrently,loss of LKB1 in DCs enhances their capacity to promote output of regulatory T cells(Tregs)from the thymus,which dominates the outcome of peripheral immune responses,as suggested by in creased resista nee to asthma and higher susceptibility to cancer in CD11 cALKB1 mice.Mechanistically,we find that loss of LKB1 specifically primes thymic CD11b+DCs to facilitate thymic Treg development and expansion,which is independent from AMPK signalling,but dependent on mTOR and enhanced phospholipase C P1-driven CD86 expression.Together,our results identify LKB1 as a critical regulator of DC-driven effector T cell and Treg responses both in the periphery and the thymus.

关 键 词：LKB1 EXPRESSED governs thymus-derived 

分 类 号：Q[生物学]