Volume 29, No 5, May 2019
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 29 Issue 5, May 2019: 391-405
ORIGINAL ARTICLES
LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity
Yanyan Wang1 , Xingrong Du 1 , Jun Wei1 , Lingyun Long1 , Haiyan Tan 2,3 , Cliff Guy 1 , Yogesh Dhungana1 , Chenxi Qian 1,4 , Geoffrey Neale5 , Yang-Xin Fu 6 , Jiyang Yu4 , Junmin Peng 2,3 and Hongbo Chi 1
1Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; 2Departments of Structural Biology and Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; 3Center for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; 4Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; 5Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA and 6Department of Pathology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA
Correspondence: Hongbo Chi (hongbo.chi@stjude.org)
Dendritic cells (DCs) play a pivotal role in priming adaptive immunity. However, the involvement of DCs in controlling excessive and deleterious T cell responses remains poorly defined. Moreover, the metabolic dependence and regulation of DC function are unclear. Here we show that LKB1 signaling in DCs functions as a brake to restrain excessive tumor-promoting regulatory T cell (Treg) and Th17 cell responses, thereby promoting protective anti-tumor immunity and maintaining proper immune homeostasis. LKB1 deficiency results in dysregulated metabolism and mTOR activation of DCs. Loss of LKB1 also leads to aberrant DC maturation and production of cytokines and immunoregulatory molecules. Blocking mTOR signaling in LKB1-deficient DCs partially rectifies the abnormal phenotypes of DC activation and Treg expansion, whereas uncontrolled Th17 responses depend upon IL-6–STAT3 signaling. By coordinating metabolic and immune quiescence of DCs, LKB1 acts as a crucial signaling hub in DCs to enforce protective anti-tumor immunity and normal immune homeostasis.
https://doi.org/10.1038/s41422-019-0157-4
FULL TEXT | PDF
Browse 825
