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TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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Modulation of T lymphocyte function by the pregnane X receptor.

Sandrine Dubrac1, Andreas Elentner, Susanne Ebner

  • 1Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.

Journal of Immunology (Baltimore, Md. : 1950)
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The pregnane X receptor (PXR) regulates T lymphocyte immune responses. PXR activation suppresses T cell proliferation and cytokine production, revealing a novel immune-regulatory role.

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Retroviral Transduction of Helper T Cells as a Genetic Approach to Study Mechanisms Controlling their Differentiation and Function

Published on: November 4, 2016

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • The pregnane X receptor (PXR) is a transcription factor involved in drug and hormone metabolism.
  • PXR expression in peripheral blood mononuclear cells (PBMCs) has been reported, but its function in immune cells is unclear.

Purpose of the Study:

  • To investigate the role of PXR in T lymphocyte function and immune regulation.

Main Methods:

  • Examined PXR expression in activated mouse and human T lymphocytes.
  • Assessed the effects of PXR activation on T lymphocyte proliferation, CD25 and IFN-gamma expression, and signaling pathways (NF-kappaB, MEK1/2).
  • Studied PXR-deficient mice to evaluate T lymphocyte responses.

Main Results:

  • PXR expression increased in activated T lymphocytes.
  • Pharmacologic PXR activation inhibited T lymphocyte proliferation, reduced CD25 and IFN-gamma levels, and decreased phosphorylated NF-kappaB and MEK1/2.
  • PXR activation increased suppressor of cytokine signaling 1 (SOCS1) expression.
  • PXR-deficient T lymphocytes showed enhanced proliferation, increased CD25 and IFN-gamma, and reduced IL-10 production.

Conclusions:

  • PXR plays a novel immune-regulatory role in T lymphocytes.
  • PXR activation suppresses T lymphocyte proliferation and function, partly via SOCS1 induction.
  • PXR deficiency leads to exaggerated T lymphocyte activation and altered cytokine profiles.