LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity
Autor: | Yang Xin Fu, Jiyang Yu, Lingyun Long, Cliff Guy, Geoffrey Neale, Haiyan Tan, Yanyan Wang, Jun Wei, Yogesh Dhungana, Junmin Peng, Xingrong Du, Chenxi Qian, Hongbo Chi |
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Rok vydání: | 2019 |
Předmět: |
0303 health sciences
Regulatory T cell Cellular differentiation T cell hemic and immune systems chemical and pharmacologic phenomena Cell Biology Dendritic cell Biology Acquired immune system Article Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system medicine Signal transduction Molecular Biology 030217 neurology & neurosurgery PI3K/AKT/mTOR pathway 030304 developmental biology |
Zdroj: | Cell Res |
ISSN: | 1748-7838 1001-0602 |
Popis: | 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. |
Databáze: | OpenAIRE |
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