| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Research Abstract |
CD26 is a costimulatory molecule preferentially expressed on memory T cells and binds to caveolin-1 of antigen presenting cells (APCs). CD26+T cells with strong migratory ability through endothelial cells play a pivotal role in inflammation and host-defense. We have studied clinical implications of the immune response mediated by CD26-caveolin-1 interaction in immune-mediated disorders.
Following CD26-caveolin-1 interaction on antigen-loaded monocytes, caveolin-1 is phosphorylated, with linkage to NF-kB activation, followed by upregulation of CD86. These responsiveness are differentially regulated by immunological conditions such as disease activity and therapy in rheumatoid arthritis(RA), systemic lupus erythematosus (SLE) and HIV infection. Decreased expression of caveolin-1 on antigen-stimulated APCs correlated with suppression of CD86 expression and enhanced T cell proliferative response by CD26-caveolin-1 interaction in immune-mediated disorders. In addition, caveolin-1 could trigger T cell activation via dimeric CD26, not monomeric CD26, in association with CARMA1 through the cytoplasmic tail of CD26.
Decreased serum soluble CD26 found in active RA and SLE patients was recovered after effective therapy, which might be related the level of CD86 expression on APCs after incorporation of soluble CD26 through caveolin-1. Furthermore, immunohistochemical studies of the rheumatoid synovium revealed an infiltration of CD26+T cells in the sublining region and high expression of caveolin-1 in the increased vasculature and synoviocytes. Soluble CD26 detected in synovial fluid might affect the expression of CD86 on caveolin-1 positive cells, and antigen-specific T cell response via CD26-caveolin-1 interaction play a pathophysiological role in rheumatoid synovium. We are planning to develop novel therapeutic approaches targeting to CD26-caveolin-1 interaction.
|
