IL‐7 downregulates IL‐7Rα expression in human CD8 T cells by two independent mechanisms

@article{Ghazawi2013IL7DI,
  title={IL‐7 downregulates IL‐7R$\alpha$ expression in human CD8 T cells by two independent mechanisms},
  author={Feras M. Ghazawi and Elliott M. Faller and Scott M. Sugden and Juzer A. Kakal and Paul A Macpherson},
  journal={Immunology and Cell Biology},
  year={2013},
  volume={91}
}
Interleukin (IL)‐7 is an essential nonredundant cytokine, and throughout the lifespan of a T‐cell signaling via the IL‐7 receptor influences cell survival, proliferation and differentiation. It is therefore no surprise that expression of the IL‐7 receptor alpha‐chain (CD127) is tightly regulated. We have previously shown that IL‐7 downregulates expression of CD127 at the cell surface and now elucidate the kinetics of that suppression and demonstrate that IL‐7 downregulates CD127 transcripts and… 
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IL‐7 induces clathrin‐mediated endocytosis of CD127 and subsequent degradation by the proteasome in primary human CD8 T cells
TLDR
It is shown for the first time in primary human CD8 T cells that upon stimulation with IL‐7, CD127 is internalized through clathrin‐coated pits, a process dependent on both lipid‐raft formation and the activity of dynamin.
IL‐7 induces sCD127 release and mCD127 downregulation in human CD8+ T cells by distinct yet overlapping mechanisms, both of which are impaired in HIV infection
TLDR
Expression of mCD127 and sCD127 is regulated by distinct, but overlapping, mechanisms and their impairment in HIV infection contributes to the understanding of the CD8+ T cell dysfunction that persists despite effective antiretroviral therapy.
Transcriptional regulation of the IL-7Rα gene by dexamethasone and IL-7 in primary human CD8 T cells
TLDR
This study cloned the CD127 gene promoter and identified key cis-regulatory elements required for CD127 expression in mature resting primary CD8 T cells and identified a suppressive region that lies upstream of 1760 bp from the TATA box, which is likely involved in the IL-7-mediated suppression of CD127 transcription.
Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells.
Jak/STAT and PI3K signaling pathways have both common and distinct roles in IL‐7‐mediated activities in human CD8+ T cells
TLDR
This study has linked STAT5 and PI3K activation to shared and distinct IL‐7‐associated activities in human CD8+ T cells and suggests a complex control of IL‐ 7‐ associated activities in the absence of antigen stimulation.
Interleukin‐7 augments CD8+ T cells function and promotes viral clearance in chronic hepatitis C virus infection
Interleukin‐7 in the transition of bone marrow progenitors to the thymus
TLDR
Mixed bone marrow chimeras demonstrated that IL‐7 signaling has a cell‐intrinsic role in ETP development but was not required for development of bone marrow progenitors, indicating that the development of ETPs is sensitive toIL‐7.
CD28-ζ CAR T Cells Resist TGF-β Repression through IL-2 Signaling, Which Can Be Mimicked by an Engineered IL-7 Autocrine Loop.
Distinct IL‐7 signaling in recent thymic emigrants versus mature naïve T cells controls T‐cell homeostasis
TLDR
It is indicated that IL‐7 responsiveness in RTE is designed to maximize survival at the expense of reduced proliferation, consistent with RTE serving as a subpopulation of T cells rich in diversity but not in frequency.
IL-7 Receptor Recovery on CD8 T-Cells Isolated from HIV+ Patients Is Inhibited by the HIV Tat Protein
TLDR
It is shown that when CD8 T-cells isolated from HIV+ patients are incubated alone in fresh medium, low CD127 expression on the cell surface recovers to normal levels, but this recovery of CD127, however, is completely inhibited by the addition of HIV Tat protein to the culture media.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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