Systemic lupus erythematosus (SLE) afflicts more than a million Americans, primarily women, and presents with symptoms resulting from the involvement of practically every organ. The origin of the disease involves diverse factors which probably contribute variably to the expression of the disease in each patient. Understanding of the molecular underpinnings that lead to an aberrant immune response through this line of research has helped us identify novel treatment targets and biomarkers. Engagement of the CD3/T cell receptor complex in SLE T cells results in early and enhanced signaling response which has been linked to decreased presence of the CD3?, aggregated lipid rafts and increased expression of the adhesion molecule CD44. Study of CD3? deficient mice revealed parallels to human SLE T cells and a noted infiltration of T cells in to various tissues including the kidney. The new information compelled the address the testable hypothesis that decreased expression of CD3? in T cells forces the formation of aggregated lipid rafts, the expression of CD44, the production of interferon-? and the ability to infiltrate target tissues. I two sets of experiments using novel engineered mice we will understand the mechanisms whereby decreased or absent expression of CD3? renders T cells able to infiltrate tissues and how manipulation of lipid rafts can mitigate organ damage resulting from T cell infiltration. In parallel, in a prospective study of SLE patients the expression of CD44 and the use of a homemade expression array of genes claimed important in the immunopathogenesis of SLE will be test their ability to serve as disease biomarkers. The significance of the proposed studies lies with the identification of novel targets and the development of biomarkers. The study of the contribution of T cells to tissue inflammation in SLE using novel engineered mice presents a unique opportunity. Furthermore, the use of our gene expression array opens the way to personalized approach to SLE.
Systemic lupus erythematosus afflicts more than a million Americans, primarily women, and presents with symptoms resulting from the involvement of practically every organ. The origin of the disease involves diverse factors which probably contribute variably to the expression of the disease in each patient. Understanding of the molecular underpinnings that lead to an aberrant immune response through this line of research will help us identify novel treatment targets and biomarkers.
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