Control of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells

Song Chen, Lijun Fang, Wei Guo, Yushan Zhou, Gang Yu, Wenwen Li, Kui Dong, Jingru Liu, Yuechen Luo, Bing Wang, Zhonglong Li, Chunxiao Zhao, Zhina Sun, Yue Shen, Qibing Leng, Dongming Zhou, Zhongchao Han, Huifang Huang, He Ren (), Guogang Xu () and Xiaoming Feng ()
Additional contact information
Lijun Fang: Chinese Academy of Medical Sciences & Peking Union Medical College
Wei Guo: Chinese Academy of Medical Sciences & Peking Union Medical College
Yushan Zhou: The Second Affiliated Hospital of Nanchang University
Gang Yu: The Second Affiliated Hospital of Nanchang University
Wenwen Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Kui Dong: Chinese Academy of Medical Sciences & Peking Union Medical College
Jingru Liu: The Union Hospital of Fujian Medical University
Yuechen Luo: Chinese Academy of Medical Sciences & Peking Union Medical College
Bing Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Zhonglong Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Chunxiao Zhao: Chinese Academy of Medical Sciences & Peking Union Medical College
Zhina Sun: Chinese Academy of Medical Sciences & Peking Union Medical College
Yue Shen: Chinese Academy of Medical Sciences & Peking Union Medical College
Qibing Leng: Shanghai Institute for Biological Sciences, Chinese Academy of Sciences
Dongming Zhou: Shanghai Institute for Biological Sciences, Chinese Academy of Sciences
Zhongchao Han: Beijing Health & Biotech Group Corp. Ltd.
Huifang Huang: The Union Hospital of Fujian Medical University
He Ren: Tianjin Medical University Cancer Institute and Hospital
Guogang Xu: Chinese PLA General Hospital
Xiaoming Feng: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract To balance immunity and tolerance, the endogenous pool of Foxp3+ regulatory T (Treg) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of Treg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive Treg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, Treg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in Treg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling Treg cell homeostasis, immune response and tolerance.

Date: 2018
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DOI: 10.1038/s41467-018-07545-8

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