Leading the way to a cure


Role of EBI2 in the Development of Murine Lupus

Gatto, Dominique, PhD

Garvan Institute of Medical Research (Darlinghurst, Australia)

The ability of the immune system to fight infection relies on the ability of immune cells to move within organs, so that they can encounter invading pathogens. Immune system cells are guided in this migration by so-called homing receptors, which recognize localization signals. While this receptor family plays an essential role in directing the movement of white blood cells for efficient responses against pathogens, dysregulation of homing receptors can result in the initiation or progression of autoimmune disorders like lupus. Thus, identifying and characterizing molecules that regulate immune cell localization is crucial to our understanding of the causes of lupus and its complications. 

Dr. Gatto and her team have found that Epstein-Barr virus-induced gene 2 (EBI2) receptors, found on white blood cells, are required for the correct migration of lymphocytes (immune system cells) during the immune response. However, people with lupus have lower levels of these receptors. Could the low levels of these receptors somehow play a role in the development of the disease? To find out, Dr. Gatto and her team will use their ALR grant to better understand how EBI2 receptors are involved in the migration of immune cells and the relevance of these receptors and the gene that encodes for them in lupus. They have created a mouse model that lacks the EBI2 gene in immune cells, mimicking low levels of EBI2 on the white blood cells of people with lupus. Their analysis will help determine if these mice are more susceptible to lupus-like disease and/or display increased production of autoantibodies, similar to what is observed in autoimmune diseases in humans.

What this study means for people with lupus: These studies will help validate the role of EBI2 in lupus and in antibody-mediated autoimmune diseases in general. This understanding might shed light on novel immunological processes that contribute to the disease, providing new approaches to treat and/or reverse the symptoms.

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