Tsc1-dependent transcriptional programming of dendritic cell homeostasis and function

Dendritic cells (DCs) are pivotal to initiating adaptive immune response. Emerging evidence highlights important roles of tuberous sclerosis complex 1 (Tsc1) in DC development and activation. Our previous study also showed that Tsc1 expression in DCs was required to promote T-cell homeostasis and re...

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Bibliographic Details
Published in:Experimental cell research 2018-02, Vol.363 (1), p.73-83
Main Authors: Luo, Yuechen, Liu, Jingru, Sun, Xiaolei, Feng, Tiantian, Fang, Lijun, Chen, Song, Fang, Chunmin, Feng, Xiaoming, Huang, Huifang
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
Antigen Presentation - immunology
ANTIGENS
CELL PROLIFERATION
DENDRITES
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - immunology
Gene Expression Regulation - drug effects
GENES
HOMEOSTASIS
Homeostasis - drug effects
Homeostasis - physiology
Mammalian target of rapamycin
Mechanistic Target of Rapamycin Complex 1 - antagonists & inhibitors
METABOLISM
Mice, Transgenic
Multiprotein Complexes - metabolism
Transcriptional regulation
Tuberous sclerosis complex 1
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary:Dendritic cells (DCs) are pivotal to initiating adaptive immune response. Emerging evidence highlights important roles of tuberous sclerosis complex 1 (Tsc1) in DC development and activation. Our previous study also showed that Tsc1 expression in DCs was required to promote T-cell homeostasis and response partially through inhibiting mammalian target of rapamycin complex1 (mTORC1). However, the molecular mechanism of transcriptional regulation by which Tsc1 control DC homeostasis and function remains largely unknown. Here we globally identified the Tsc1-regulated genes by comparing the transcriptional profiling of Tsc1-deficient DCs with wild-type DCs. It showed that Tsc1 specifically regulated the expression of groups of gene sets critically involved in DC survival, proliferation, metabolism and antigen presentation. The impacts of Tsc1 on DC gene expression were partially dependent on inhibition of mTORC1 signal. Our study thus provides a comprehensive molecular basis for understanding how Tsc1 programs the homeostasis and function of DCs through transcriptional regulation. •Transcriptional mechanisms of Tsc1-regulated DC homeostasis and function.•Tsc1 controls DC survival, proliferation, metabolism and antigen presentation.•Tsc1affect DC gene expression partially through inhibition of mTORC1 signal.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2017.12.028