Asthma is a disease of airway inflammation in which airway eosinophilia is a prominent histologic feature. Eosinophils can release toxic mediators, lipids and pro-inflammatory cytokines that can induce airway hyper- responsiveness. Identifying the mechanisms that are involved in recruiting eosinophils to the site of injury are therefore critical in the understanding of pathogenesis of disease. Chemokines are a family of secreted proteins that play a critical role in directing different types of leukocytes to the site of infection of tissue damage.
The aim of this proposal is to examine the role of Th2 cells in regulating the expression of eotaxin, a chemokine specific for eosinophils. We hope to identify and characterize molecules or factors released from Th2 cells that are responsible for affecting the expression of eotaxin at the mRNA and protein levels. We then hope to identify transcription factors that are important in promoting gene expression of eotaxin. The importance of these molecules will be examined in vivo using existing knockout animals. This work will lead to the greater understanding of the role of Th2 cells and eotaxin asthma.
| Mathew, Anuja; Medoff, Benjamin D; Carafone, Andrew D et al. (2002) Cutting edge: Th2 cell trafficking into the allergic lung is dependent on chemoattractant receptor signaling. J Immunol 169:651-5 |
| Medoff, Benjamin D; Sauty, Alain; Tager, Andrew M et al. (2002) IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol 168:5278-86 |
| Mathew, A; MacLean, J A; DeHaan, E et al. (2001) Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation. J Exp Med 193:1087-96 |
