Abstract

Asthma appears to be a disease that is driven by a predominantly Th2 immune response to environmental antigens. CD4 T cell effector responses are, however, extensively regulated under normal circumstances with Th2 responses being modulated by Th1 CD4 T cells, as well as by other mechanisms. Costimulatory molecules play a critical role in the activation and differentiation of CD4 T cells. Recently, the costimulator ICOS has been discovered to be expressed on activated T cells, where it seems to play a critical role in the differentiation of CD4 T cells to effector cells producing a number of critical cytokines such as IL4 and IL13. In this proposal, we will utilize ICOS deficient mice that were recently generated in the laboratory of the PI to elucidate the cellular and molecular mechanisms whereby ICOS regulates Th2 cytokine gene expression, and the role that ICOS plays in regulating the immune response and pathology, in ovalbumin and HDI mouse models of asthma.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL056389-06A1
Application #
6604843
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2002-04-01
Project End
2007-02-28
Budget Start
2002-04-01
Budget End
2003-02-28
Support Year
6
Fiscal Year
2002
Total Cost
$280,238
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Liu, Juan; Harberts, Erin; Tammaro, Antonella et al. (2014) IL-9 regulates allergen-specific Th1 responses in allergic contact dermatitis. J Invest Dermatol 134:1903-1911
Bhandari, Vineet; Choo-Wing, Rayman; Harijith, Anantha et al. (2012) Increased hyperoxia-induced lung injury in nitric oxide synthase 2 null mice is mediated via angiopoietin 2. Am J Respir Cell Mol Biol 46:668-76
Homer, Robert J; Elias, Jack A; Lee, Chun Gun et al. (2011) Modern concepts on the role of inflammation in pulmonary fibrosis. Arch Pathol Lab Med 135:780-8
Koh, Byung Hee; Hwang, Soo Seok; Kim, Joo Young et al. (2010) Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma. Proc Natl Acad Sci U S A 107:10614-9
Chapoval, Svetlana P; Lee, Chun Geun; Tang, Chuyan et al. (2009) Lung vascular endothelial growth factor expression induces local myeloid dendritic cell activation. Clin Immunol 132:371-84
Hartl, Dominik; He, Chuan Hua; Koller, Barbara et al. (2008) Acidic mammalian chitinase is secreted via an ADAM17/epidermal growth factor receptor-dependent pathway and stimulates chemokine production by pulmonary epithelial cells. J Biol Chem 283:33472-82
He, Chuan Hua; Waxman, Aaron B; Lee, Chun Geun et al. (2005) Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury. J Clin Invest 115:1039-48
Becker, Patrice M; Waltenberger, Johannes; Yachechko, Robin et al. (2005) Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circ Res 96:1257-65
Wisnewski, Adam V; Liu, Qing; Miller, Jing-Jing et al. (2002) Effects of hexamethylene diisocyanate exposure on human airway epithelial cells: in vitro cellular and molecular studies. Environ Health Perspect 110:901-7
Wisnewski, A V; Cain, H; Magoski, N et al. (2001) Human gamma/delta T-cell lines derived from airway biopsies. Am J Respir Cell Mol Biol 24:332-8

Showing the most recent 10 out of 13 publications