Elucidating the role of T-cell co-receptor SLAMF6/SAP signaling in SLE pathogenesis.

Systemic Lupus Erythematosus is an autoimmune disease in which cells of the immune system become hyper-active and start to attack one's own organs. T-cells are part of the immune system that normally help fight infection. T-cells are like generals responsible for directing the soldiers of the immune system to respond to infection, but in lupus the T-cell function is dysregulated to react against the self. Many of our current treatments target T-cells, but they are not specific in their function and result in unwanted side effects. In reality, there are different subtypes of T-cells: some protect from inflammation and others make it worse. We need to better understand which T-cell subsets are dysregulated and how they work, only then can we design better treatments to target specific pathways to cure lupus. In our preliminary work, we have identified a signaling pathway through a receptor, SLAMF6, and its messenger, SAP, to be increased in T cells from lupus patients as compared to healthy persons. In this application, we propose to evaluate this SLAMF6/SAP unit across different T-cell subsets, revealing the function of this receptor across the different T cells. In completing this work, we will thus define relevant pathways for future SLAMF6 targeted treatments. Additionally, we will test the theory that higher SAP levels are associated with more active lupus symptoms. If true, then blood SAP levels can be used as a rapid test to identify inflamed lupus patients with an abnormally elevated SLAMF6/SAP signal, identifying these patients as likely to improve if they receive treatment with SLAMF6-targeted treatments.