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Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct

Keunwook Lee1, Prathyusha Gudapati, Srdjan Dragovic

  • 1Department of Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Immunity
|July 13, 2010
PubMed

Insights

The mammalian target of rapamycin complex 2 (mTORC2) is crucial for T helper cell differentiation. Deleting rictor, an mTORC2 subunit, impairs Th1 and Th2 cell development by affecting protein kinase B (Akt) and PKC signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The mammalian target of rapamycin (mTOR) pathway plays critical roles in cell growth and metabolism.
  • While mTOR complex 1 (mTORC1) functions are well-studied, the biology of mTOR complex 2 (mTORC2) remains less understood.
  • mTORC2 is implicated in various cellular processes, including cytoskeletal organization and cell survival.

Purpose of the Study:

  • To investigate the role of mTORC2 in T helper cell differentiation.
  • To elucidate the specific downstream signaling pathways regulated by mTORC2 during T cell activation.
  • To determine the contribution of mTORC2 to the development of distinct T helper cell subsets.

Main Methods:

  • Conditional deletion of the rictor gene, an essential mTORC2 subunit, in mice.
  • Analysis of T helper cell differentiation (Th1, Th2, Th17, and FoxP3+ regulatory T cells).
  • Assessment of protein phosphorylation (Akt, PKC) and transcription factor activation (T-bet, GATA3, NF-kappaB) following T cell activation.

Main Results:

  • Conditional deletion of rictor impaired differentiation into T helper 1 (Th1) and T helper 2 (Th2) cells.
  • mTORC2 promoted the phosphorylation and activation of protein kinase B (PKB/Akt) and protein kinase C (PKC).
  • Restoration of Akt activity rescued Th1 differentiation (T-bet expression), while activated PKC-theta rescued Th2 differentiation (GATA3 expression).

Conclusions:

  • mTORC2 plays a vital role in regulating T helper cell differentiation.
  • Distinct mTORC2-dependent pathways involving Akt and PKC signaling control the development of Th1 and Th2 cell subsets.
  • These findings uncover crucial mTOR-Akt and mTOR-PKC connections in adaptive immunity.

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