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Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4

Anja Hilliard1, Brendan Hilliard, Shi-Jun Zheng

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|November 23, 2006
PubMed

Insights

Programmed cell death 4 (PDCD4) deficiency in mice leads to spontaneous lymphomas but resistance to autoimmune diseases. PDCD4 regulates protein translation in the immune system, controlling both cancer and inflammation.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Heightened protein translation is linked to cancer and inflammatory diseases.
  • Mechanisms of translational regulation and the role of translation factors in disease remain unclear.
  • Programmed cell death 4 (PDCD4) is identified as a novel inhibitor of protein translation.

Purpose of the Study:

  • To investigate the in vivo roles of PDCD4 in disease pathogenesis.
  • To determine the function of PDCD4 in regulating protein translation within the immune system.

Main Methods:

  • Generation of PDCD4-deficient mice using gene targeting.
  • Analysis of tumor development, lifespan, and immune responses in PDCD4-deficient mice.
  • Mechanistic studies on lymphocyte activation and cytokine production.

Main Results:

  • PDCD4-deficient mice developed spontaneous lymphomas, primarily of B lymphoid origin, with metastasis.
  • These mice exhibited reduced lifespan but showed resistance to inflammatory diseases like autoimmune encephalomyelitis and diabetes.
  • PDCD4-deficient lymphocytes produced cytokines that promoted oncogenesis while suppressing inflammation.

Conclusions:

  • PDCD4 plays a critical role in controlling lymphoma genesis by inhibiting protein translation.
  • PDCD4 is essential for regulating autoimmune inflammation within the immune system.
  • Selective inhibition of protein translation by PDCD4 impacts both cancer development and inflammatory responses.

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