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Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
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Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells

Hirotoshi Kawashima1, Hiroaki Takatori, Kotaro Suzuki

  • 1Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|September 6, 2013
PubMed

Insights

The tumor suppressor p53, crucial for preventing cancer, also prevents autoimmune diseases. This study shows p53 in T cells is vital for regulatory T cell development, suppressing autoimmunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The tumor suppressor p53 is known for its role in preventing cancer.
  • Emerging evidence suggests p53 also suppresses autoimmune diseases, but the mechanism is unclear.

Purpose of the Study:

  • To investigate the role of T cell-specific p53 in autoimmunity.
  • To elucidate the mechanism by which p53 suppresses autoimmune responses.

Main Methods:

  • Generation of T cell-specific p53-deficient mice (CD4-Cre p53(fl/fl) or p53 cKO).
  • Analysis of autoimmune phenotypes, autoantibodies, and regulatory T cell (Treg) populations in p53-cKO mice.
  • Investigation of p53's effect on Foxp3 gene transcription.

Main Results:

  • Aged p53-cKO mice developed spontaneous inflammatory lesions and autoantibodies.
  • A significant reduction in regulatory T cells (Tregs) was observed in p53-cKO mice.
  • p53 was found to enhance Foxp3 transcription by binding to its regulatory regions.

Conclusions:

  • T cell-expressed p53 suppresses autoimmunity.
  • p53 is essential for the differentiation and maintenance of regulatory T cells.
  • p53 acts as an autoimmune suppressor by promoting Treg induction through Foxp3 gene regulation.

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