LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity

Yanyan Wang, Xingrong Du, Jun Wei, Lingyun Long, Haiyan Tan, Cliff Guy, Yogesh Dhungana, Chenxi Qian, Geoffrey Neale, Yang Xin Fu, Jiyang Yu, Junmin Peng, Hongbo Chi

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)391-405
Number of pages15
JournalCell Research
Volume29
Issue number5
DOIs
StatePublished - May 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Wang, Y., Du, X., Wei, J., Long, L., Tan, H., Guy, C., Dhungana, Y., Qian, C., Neale, G., Fu, Y. X., Yu, J., Peng, J., & Chi, H. (2019). LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity. Cell Research, 29(5), 391-405. https://doi.org/10.1038/s41422-019-0157-4