LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity.

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.

journal_name

Cell Res

journal_title

Cell research

authors

Wang Y,Du X,Wei J,Long L,Tan H,Guy C,Dhungana Y,Qian C,Neale G,Fu YX,Yu J,Peng J,Chi H

doi

10.1038/s41422-019-0157-4

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

391-405

issue

5

eissn

1001-0602

issn

1748-7838

pii

10.1038/s41422-019-0157-4

journal_volume

29

pub_type

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