TSC1/2 Signaling Complex Is Essential for Peripheral Naïve CD8+ T Cell Survival and Homeostasis in Mice

@article{Zhang2012TSC12SC,
  title={TSC1/2 Signaling Complex Is Essential for Peripheral Na{\"i}ve CD8+ T Cell Survival and Homeostasis in Mice},
  author={Lianjun Zhang and Hongbing Zhang and Lanlan Li and Yi Xiao and En Y Rao and Zhuang Miao and Hui Chen and Lina Sun and Hongran Li and Guangwei Liu and Yong Zhao},
  journal={PLoS ONE},
  year={2012},
  volume={7}
}
The PI3K-Akt-mTOR pathway plays crucial roles in regulating both innate and adaptive immunity. However, the role of TSC1, a critical negative regulator of mTOR, in peripheral T cell homeostasis remains elusive. With T cell-specific Tsc1 conditional knockout (Tsc1 KO) mice, we found that peripheral naïve CD8+ T cells but not CD4+ T cells were severely reduced. Tsc1 KO naïve CD8+ T cells showed profound survival defect in an adoptive transfer model and in culture with either stimulation of IL-7… Expand
TSC1 regulates the balance between effector and regulatory T cells.
TLDR
It is suggested that TSC1 acts as an important checkpoint for maintaining immune homeostasis by regulating cell fate determination by regulating mTOR pathway regulation. Expand
TSC 1 regulates the balance between effector and regulatory T cells
Mammalian target of rapamycin (mTOR) plays a crucial role in the control of T cell fate determination; however, the precise regulatory mechanism of the mTOR pathway is not fully understood. We foundExpand
Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+CD25+Foxp3+ regulatory T‐cell development in mice
  • Hui Chen, L. Zhang, +9 authors Y. Zhao
  • Biology, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2013
TLDR
The studies suggest that TSC1 plays an important role in regulating thymic CD4+CD25+Foxp3+ nTreg‐cell development via a Rapa‐resistant and mTORC2‐dependent signaling pathway. Expand
Role of Tumor Suppressor TSC1 in Regulating Antigen-Specific Primary and Memory CD8 T Cell Responses to Bacterial Infection
TLDR
Findings provide direct evidence of a CD8 T cell-intrinsic role for TSC1 in the regulation of antigen-specific primary and memory responses to bacterial infection. Expand
Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner.
TLDR
It is shown that mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions. Expand
TSC1 controls IL-1β expression in macrophages via mTORC1-dependent C/EBPβ pathway
TLDR
It is found that TSC1 deficiency resulted in impaired expression of pro-IL-1β in macrophages following lipopolysaccharide stimulation, and mechanism studies suggest that mTORC1-mediated downregulation of the CCAAT enhancer-binding protein (C/EBPβ) critically contributes to the defective pro- IL-1 β expression. Expand
mTORC 1 and mTORC 2 selectively regulate CD 8 + T cell differentiation
Activation of mTOR-dependent pathways regulates the specification and differentiation of CD4+ T effector cell subsets. Herein, we show that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles inExpand
mTORC1 and mTORC2 selectively regulate CD8⁺ T cell differentiation.
TLDR
It is shown that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles in the generation of CD8+ T cell effector and memory populations and suggest that these functions have the potential to be targeted for enhancing vaccine efficacy and antitumor immunity. Expand
Mammalian Target of Rapamycin Complex 1 Orchestrates Invariant NKT Cell Differentiation and Effector Function
TLDR
Using mice with T cell–restricted deletion of Raptor, it is shown that mTORC1 is selectively required for iNKT but not for conventional T cell development, and bone marrow chimera studies demonstrate that m TORC1 controls iN KT differentiation in a cell-intrinsic manner. Expand
TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation
TLDR
It is demonstrated that both constitutive Peyer’s patch germinal centers (GCs) and immunization-induced splenic GCs are unimpaired in TSC1-deficient (TSC1KO) mice and that the ratio of GC B cells to total B cells is comparable in WT and T SC1KO mice. Expand
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References

SHOWING 1-10 OF 47 REFERENCES
The AKT–mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells
TLDR
AKT is identified as a strong repressor of entry into the T reg phenotype in vitro and in vivo and is placed at a nexus of signaling pathways whose proper activation has a strong and broad impact on the onset of T reg specification. Expand
The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin.
TLDR
It is demonstrated that interleukin-12 (IL-12) enhanced and sustained antigen and costimulatory molecule (B7.1)-induced mTOR kinase activity in naive CD8+ (OT-I) T cells via phosphoinositide 3-kinase and STAT4 transcription factor pathways. Expand
Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling
TLDR
It is demonstrated that Notch/RBP-J signaling regulates γδ T cell generation and migration, αβ T cell maturation, terminal differentiation of CD4 + T cells into Th1/Th2 cells, and activation of T cells. Expand
Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells
TLDR
It is demonstrated that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Expand
The role of mTOR in memory CD8+ T‐cell differentiation
TLDR
The role of mTOR in memory CD8+ T‐cell differentiation is reviewed and the effect of rapamycin among CD8 + T cells, CD4+ T cells and dendritic cells is compared to discuss potential application of these findings in a clinical setting. Expand
Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
TLDR
A critical role for a balance between Bim and Bcl-2 is demonstrated in controlling homeostasis of naive and memory T cells in mice deficient in one or both alleles of Bim. Expand
IL-7 promotes T cell proliferation through destabilization of p27Kip1
TLDR
IL-7 maintains T cell proliferation through a novel pathway of p27Kip1 regulation, and evidence suggests that PKCθ acts via a distinct, unknown pathway inducing G1 arrest after IL-7 withdrawal from T cells. Expand
The TSC-mTOR signaling pathway regulates the innate inflammatory response.
TLDR
It is shown that the tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) pathway regulated inflammatory responses after bacterial stimulation in monocytes, macrophages, and primary dendritic cells, and protected genetically susceptible mice against lethal Listeria monocytogenes infection. Expand
Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling.
TLDR
It is demonstrated that Notch/RBP-J signaling regulates gammadelta T cell generation and migration, alphabeta T cell maturation, terminal differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells. Expand
Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo
The naïve and memory T lymphocyte pools are maintained through poorly understood homeostatic mechanisms that may include signaling via cytokine receptors. We show that interleukin-7 (IL-7) playsExpand
...
1
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3
4
5
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