Leading the way to a cure


Antigen Trafficking Between APCs as a Therapeutic Target for SLE

Mamula, Mark, PhD

Yale University

Specialized immune cells called antigen-presenting cells (APCs) play a role in directing immunity against self-antigens, the process that leads to lupus and other autoimmune conditions. One type of APC are B cells, which not only have a unique ability to capture specific proteins but also play an important role in the underlying pathogenesis of lupus. Although we don’t yet know exactly how B cells trigger lupus, one theory suggests that it may be related to the way in which B cells bind specific self antigens then transfer them to other APCs. This would result in a strong autoimmune response against the known lupus antigens.

Dr. Mamula and his team have conducted research showing that human B cells do, indeed, transfer antigens to other APCs called dendritic cells. These cells “turn up the volume,” or amplify, the autoimmune response. The researchers have also identified a receptor on the surface of APC cells called Scavenger Receptor A (SR-A) that enables this process to occur.

With their ALR grant, Dr. Mamula and his team will try and identify small molecules that block the SR-A surface protein. These antagonists would prevent autoimmune antigens from connecting with and entering the cell, thus inhibiting the autoimmune response. The researchers also plan to evaluate the role of this antigen transfer in the development of lupus by studying lupus-prone mice who do not express the SR-A protein. In these studies, they also hope to learn more about the timing of antigen transfer from human B cells to APCs in the presence of SR-A inhibitors, and evaluate the ability of SR-A inhibitors to block autoimmunity

What this study means for people with lupus: This study will help determine if SR-A is a potential therapeutic target to prevent lupus autoimmunity. The small molecule inhibitors identified by these studies should be potential therapeutic candidates for the treatment of lupus.

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