Solute carrier family 15 member 4, an emerging therapeutic target for systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) and autoantibodies with limited effective clinical treatments. Solute carrier family 15 member 4 (SLC15A4), a proton-coupled oligopeptide transporter, facilitates the transmembrane transport of L-histidine and some di- and tripeptides from the lysosome to the cytosol. A growing body of evidence has elucidated the critical role of SLC15A4 in pathogenesis and disease progression of SLE. Genome-wide association studies have identified SLC15A4 as a new susceptibility locus of SLE. Further mechanistical studies have demonstrated that SLC15A4 involves in the production of type I IFNs in plasmacytoid dendritic cells (pDCs) and its necessity in B cells for autoantibody production in lupus models. These studies strongly support the potential of SLC15A4 as a promising therapeutic target for SLE. This review aims to summarize recent advances in understanding the role of SLC15A4 in disease progression of SLE and the development of SLC15A4-targeted inhibitors as well as discuss its potential as a target for SLE treatment.