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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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Published on: December 30, 2016

PI3-kinase and the control of T cell growth and proliferation by FoxOs

Stéphanie Fabre1, Valérie Lang, Georges Bismuth

  • 1Institut Cochin, Départment de biologie cellulaire, Inserm U567, CNRS UMR8104. Université René-Descartes, équipe labellisée par la Ligne nationale contre le cancer, 22 rue Méchain, 75014 Paris. fabre@cochin.inserm.fr

Bulletin Du Cancer
|June 17, 2006
PubMed

Insights

The PI3-kinase pathway

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • The PI3-kinase (phosphatidylinositol 3-kinase) pathway is frequently hyperactivated in various cancers, driving uncontrolled cell survival and proliferation.
  • The proto-oncogene Akt, a key effector of this pathway, regulates critical molecular switches, including the Forkhead box proteins of the O class (FoxOs).
  • FoxOs act as tumor suppressors by inhibiting cell cycle entry and promoting cell quiescence.

Purpose of the Study:

  • This mini-review aims to explore the intricate relationship between PI3-kinase signaling and FoxO transcription factors.
  • The focus is on the role of FoxOs in regulating T lymphocyte proliferation, particularly during antigen-induced clonal expansion.
  • To elucidate how PI3-kinase pathway dysregulation impacts the function of these growth-suppressive genes in T cells.

Main Methods:

  • This review synthesizes findings from recent experimental studies.
  • It focuses on evidence demonstrating the interplay between PI3-kinase/Akt signaling and FoxO activity in T lymphocytes.
  • The review discusses the molecular mechanisms linking metabolic signaling to the regulation of cell growth in immune cells.

Main Results:

  • The PI3-kinase/Akt pathway influences the activity and localization of FoxO transcription factors.
  • Aberrant PI3-kinase signaling can lead to the suppression of FoxO-mediated growth inhibition.
  • FoxOs play a crucial role in controlling the proliferative response of T cells, impacting immune cell homeostasis.

Conclusions:

  • FoxO transcription factors are critical regulators of cell cycle control and immune cell proliferation.
  • The PI3-kinase pathway significantly modulates FoxO function, with implications for cancer and immune responses.
  • Understanding this crosstalk is vital for developing targeted therapies for cancers and immune-related disorders.

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