Dissecting the role of the Lyn tyrosine kinase in B cell differentiation and the development of autoimmunity.

Funded Activity Summary

The immune system has to be capable of responding to an unlimited array of pathogens, but at the same time remain unresponsive to, or tolerant of self-antigens. A breakdown in the tolerance to self-antigens results in autoimmunity. Autoimmune diseases include more than 70 chronic disorders that affect about 1 in 20 people in the Western population. Improving our understanding of the mechanisms that underlie autoimmune disease is essential for the design of more effective treatments. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated two strains of mice, one that is unable to make Lyn (Lyn-deficient mice) and one that expresses an activated form of the Lyn enzyme (Lyn-up mice). We have found that both strains of mice develop autoimmune disease with characteristics similar to the human autoimmune disease systemic lupus erythematosus (SLE). These studies suggest that Lyn is an important severity gene in autoimmunity. In this study we will examine in detail the role that Lyn plays in B cell development, function and autoimmunity, and we intend to identify the pathways that lead to autoimmune disease in Lyn mutant mice. On completion of these studies we will have developed a catalogue of the molecules and pathways perturbed in Lyn mutant mice. These studies will greatly improve our knowledge and understanding of the mechamisms behind certain autoimmune diseases, and may indeed lead to improved diagnosis, prognosis and treatment of patients with these conditions.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $487,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Emergency medicine

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Autoantibodies and autoantigens | Autoimmune disease | Autoimmune glomerulonephritis | B cell tolerance | Lyn tyrosine kinase | Mouse models of autoimmunity | Signal transduction | Signaling pathways in autoimmunity | Systemic lupus erythematosus and Sjogren's syndrome

Related Links