Leading the way to a cure


Functional Relationships Between the Lupus Susceptibility Loci Lyn and Ets1

Satterthwaite, Anne, PhD

University of Texas Southwestern Medical Center at Dallas

A key contributor to lupus is the production of antibodies that recognize the body’s own components (autoantibodies). These antibodies, which are produced from B cell-derived plasma cells, collect in various tissues and organs, including the kidney, causing inflammation and tissue damage. 

Two genes involved in the development of lupus, Lyn and Ets1, limit production of these plasma cells in mice. Without either of those genes, mice develop a lupus-like autoimmune disease. Dr. Satterthwaite, her colleague Lee Ann Garrett-Sinha, PhD, and their teams have shown that B cells that lack Lyn also have reduced Ets1 levels, suggesting that the two genes operate in a common pathway to control the development of plasma cells and the production of autoantibodies. 

With their grant, they will test the hypothesis that Lynnormally prevents autoantibody production by promoting the expression of the Ets1 protein. Among the questions they will explore: 

• Does Lyn act in B cells or some other cell type to control Ets1expression? 

• Which pathways regulated by Lyn are involved in altering Ets1 expression?

• Does Lyn control the expression of the Ets1 gene or regulate the stability of the Ets1 protein? 

They will also explore the consequences of reduced Ets1levels in Lyn-deficient B cells, and determine whether low levels of Lyn and Ets1 together contribute to the development of autoimmunity. They will also restore normal Ets1 levels in Lyn-deficient B cells to see if this prevents autoantibody production. 

What this study means for people with lupus: Defining and characterizing this novel pathway may reveal new therapeutic targets that could prevent the antibody-related tissue damage.

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