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TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses

R Tomasini1, V Secq, L Pouyet

  • 1INSERM U1068, CRCM, Stress Cellulaire, 163 Avenue de Luminy, Case 915, Parc de Luminy, 13288 Marseille Cedex 9, France. richard.tomasini@inserm.fr

Cell Death and Differentiation
|September 15, 2012
PubMed

Insights

The TAp73 protein plays a crucial role in innate immunity and septic shock by regulating macrophage polarization. Its absence leads to prolonged inflammation and increased mortality during lipopolysaccharide challenges.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The p73 protein, a member of the p53 family, exists in multiple isoforms with diverse functions.
  • While p73 isoforms modulate p53 activity, their specific roles in innate immunity and septic shock remain unclear.
  • Previous studies implicated p73 isoforms in tumor suppression, DNA damage response, and development.

Purpose of the Study:

  • To investigate the role of TAp73 in innate immunity and its contribution to septic shock.
  • To elucidate the impact of TAp73 deficiency on macrophage function and inflammatory responses.
  • To determine if TAp73 influences macrophage polarization during innate immune challenges.

Main Methods:

  • Utilized TAp73 knockout (TAp73(-/-)) and wild-type mice subjected to lipopolysaccharide (LPS) challenge.
  • Assessed inflammatory cytokine levels, mortality rates, and macrophage behavior (cytokine production, phagocytosis, MHC class II expression) in vitro.
  • Investigated the effect of TAp73-deficient macrophages on LPS-induced septic shock in vivo.

Main Results:

  • TAp73(-/-) mice exhibited increased mortality and elevated blood levels of proinflammatory cytokines (TNF-α, IL-6, MIP-2) after LPS challenge.
  • TAp73(-/-) macrophages showed enhanced pro-inflammatory cytokine production, prolonged survival, impaired phagocytosis, and increased MHC class II expression.
  • Mice reconstituted with TAp73(-/-) macrophages displayed heightened sensitivity to LPS, indicating a critical role for TAp73 in macrophage-mediated immunity.

Conclusions:

  • TAp73 is essential for regulating macrophage polarization during innate immune responses.
  • Absence of TAp73 leads to a prolonged M1 effector phenotype and impaired resolution of inflammation, contributing to septic shock.
  • TAp73 plays a significant role in innate immunity, influencing macrophage function and inflammatory responses.

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