title: Transgenic expression of survivin compensates for OX40-deficiency in driving Th2 development and allergic inflammation.
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.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Fengyang
authors.initials: F
authors.lastname: Lei
authors.forename: Jianyong
authors.initials: J
authors.lastname: Song
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xiong
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: Lens
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Jianxun
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D053262:Receptors, OX40 / Q000172:deficiency / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology* / Q000378:metabolism; D000077022:Survivin; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D053262:Receptors, OX40; D012097:Repressor Proteins; D000077022:Survivin; C505717:Tnfrsf4 protein, mouse
keywords: Costimulation; Lung inflammation; Murine model; Survivin; Th2 cells