Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 7, Pages 1914-1924Publisher
WILEY
DOI: 10.1002/eji.201243081
Keywords
Costimulation; Lung inflammation; Murine model; Survivin; Th2 cells
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Funding
- National Institute of Health [K18CA151798, R01AI079056]
- Pennsylvania Department of Health
- Dutch Cancer Society [UU2009-4311, UU2011-5143]
- Netherlands Organization for Scientific Research [NWO Vici 918.12.610]
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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.
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