Back to Search
Start Over
LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity.
- Source :
-
Cell research [Cell Res] 2019 May; Vol. 29 (5), pp. 391-405. Date of Electronic Publication: 2019 Mar 25. - Publication Year :
- 2019
-
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.
- Subjects :
- AMP-Activated Protein Kinases
Animals
Cell Differentiation
Cell Line, Tumor
Dendritic Cells cytology
Interferon-gamma metabolism
Interleukin-17 metabolism
Interleukin-6 metabolism
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms immunology
Neoplasms pathology
Protein Serine-Threonine Kinases deficiency
Protein Serine-Threonine Kinases genetics
STAT3 Transcription Factor metabolism
Signal Transduction
T-Lymphocytes, Regulatory cytology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
TOR Serine-Threonine Kinases antagonists & inhibitors
TOR Serine-Threonine Kinases metabolism
Th17 Cells cytology
Th17 Cells metabolism
Thymus Gland metabolism
Dendritic Cells metabolism
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1748-7838
- Volume :
- 29
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell research
- Publication Type :
- Academic Journal
- Accession number :
- 30911060
- Full Text :
- https://doi.org/10.1038/s41422-019-0157-4