Potential Therapeutic Roles Of Lysophospholipid Signaling In Autoimmune-Related Disease

Abstract

Autoimmune disorders are characterized by lymphocyte infiltration and destruction of affected tissues. Lysophospholipids are small, relatively simple phospholipids derived from cell membranes that have been shown over the last decade to produce a wide range of effects through cognate G protein-coupled receptors, and include sphingosine 1-phosphate (S1P), which is the focus of this review, as well as lysophosphatidic acid (LPA). S1P1, a sphingosine 1-phosphate lysophospholipid receptor, is essential for lymphocyte egress from the thymus and peripheral lymphoid tissues. Here we review how changes in S1P1-receptor expression and S1P concentration affect lymphocyte trafficking. In particular, we focus on mechanisms that involve S1P1 through its removal via genetic deletion and inhibition via pharmacological intervention, which provide a foundation for potentially useful approaches to the treatment of autoimmune disease based on lysophospholipid signaling modulation. Recent advances in our understanding of how...