Autotaxin may play a Critical Role between the Genetic Risk Factors and Pathogenesis of SLE in Plasmacytoid Dendritic Cells

The importance of autotaxin, which catalyzes the production of lysophospholipids, has recently been recognized in various diseases including cancer and autoimmune diseases. We herein report our analysis of autotaxin in systemic lupus erythematosus (SLE), utilizing data from ImmuNexUT, a comprehensive database consisting of transcriptome data and expression quantitative trait locus (eQTL) data of immune cells from patients with immune-mediated disorders. Autotaxin was elevated in the serum of SLE patients, and the expression of ENPP2, which encodes autotaxin, is elevated in plasmacytoid dendritic cells (pDCs) of SLE patients compared to healthy controls. In weighted correlation network analysis, ENPP2 belonged to a module that correlated with disease activity. This module was enriched in interferon-associated genes and included genes whose expression is influenced by SNPs associated with SLE, suggesting that it is a key module connecting genetic risk factors of SLE with disease pathogenesis. The increased expression of ENPP2 in pDCs from SLE patients may be due to increased expression of interferon-associated genes and increased binding of STAT3 complexes to the regulatory region of ENPP2. Thus, autotaxin may play a critical role in connecting genetic risk factors of SLE to disease pathogenesis in pDCs.