Transgenic expression of survivin compensates for OX40-deficiency in driving Th2 development and allergic inflammation

Fengyang Lei, Jianyong Song, Rizwanul Haque, Xiaofang Xiong, Deyu Fang, Yuzhang Wu, Susanne M.A. Lens, Michael Croft, Jianxun Song

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Survivin, an inhibitor of apoptosis family molecule, has been proposed as a crucial intermediate in the signaling pathways leading to T-cell development, proliferation, and expansion. However, the importance of survivin to T-cell-driven inflammatory responses has not been demonstrated. Here, we show that survivin transgenic mice exhibit an increased antigen-driven Th2 lung inflammation and that constitutive expression of survivin reversed the defective lung inflammation even in the absence of OX40 costimulation. We found that OX40-deficient mice were compromised in generating Th2 cells, airway eosinophilia, and IgE responses. In contrast, OX40-deficient/survivin transgenic mice generated normal Th2 responses and exhibited strong lung inflammation. These results suggest that OX40 costimulation crucially engages survivin during antigen-mediated Th2 responses. These findings also promote the notion that OX40 costimulation regulates allergic responses or lung inflammation by targeting survivin thereby enhancing T-cell proliferation and resulting in more differentiated Th2 cells in the allergic inflammatory response.

Original languageEnglish (US)
Pages (from-to)1914-1924
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • Costimulation
  • Lung inflammation
  • Murine model
  • Survivin
  • Th2 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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