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Related Experiment Videos

Pin1 modulates the type 1 immune response.

Stephane Esnault1, Ruedi K Braun, Zhong-Jian Shen

  • 1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.

Plos One
|February 22, 2007
PubMed
Summary
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Pin1 regulates T cell cytokine production and transplant rejection. Pin1 inhibitors show promise as immunosuppressants, potentially enhancing current therapies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Transplantation Science

Background:

  • T cell receptor (TCR) and costimulatory molecule signaling control cytokine production.
  • Calcineurin and NF-AT are key transcriptional regulators, antagonized by PPIases like cyclophilin A and FKBP.
  • The role of downstream signaling molecules in cytokine mRNA stabilization remains largely undefined.

Purpose of the Study:

  • To investigate the role of Pin1, a peptidyl-prolyl isomerase (PPIase), in the post-transcriptional regulation of T cell cytokine production.
  • To evaluate the therapeutic potential of Pin1 inhibition in preventing transplant rejection.

Main Methods:

  • Pharmacologic and genetic blockade of Pin1 in activated T cells.
  • Assessment of Th1 cytokine mRNA stability, accumulation, and protein expression.

Related Experiment Videos

  • In vivo studies using MHC mismatched orthotopic rat lung transplant models.
  • Combined blockade with cyclosporine A and a Pin1 inhibitor (juglone).

    • Main Results:

    • Pin1 mediates post-transcriptional regulation of Th1 cytokines (IFN-gamma, IL-2, CXCL-10) in activated T cells.
    • Pin1 blockade significantly reduced cytokine mRNA stability, accumulation, and protein levels.
    • In vivo, Pin1 blockade prevented acute and chronic lung transplant rejection by decreasing IFN-gamma and CXCL-10 expression.
    • Combined inhibition of Pin1 and calcineurin showed synergistic effects.

    Conclusions:

    • Pin1 is a critical regulator of T cell-mediated immune responses and transplant outcomes.
    • Pin1 inhibitors represent a potential new class of immunosuppressants.
    • Combination therapy with Pin1 inhibitors and calcineurin inhibitors may reduce toxicity and improve efficacy.