Taurine Metabolism Aggravates the Progression of Lupus by Promoting the Function of Plasmacytoid Dendritic Cells

Objective Type I interferons (IFNs) are critical in the development of systemic lupus erythematosus (SLE). Metabolic abnormalities cause dysregulation of multiple immune cells, but the metabolic regulation of type I IFN production is not well clarified in SLE. We undertook this study to define amino acid metabolism features in SLE and to explore the function of disease‐relevant metabolites in the control of plasmacytoid dendritic cell (pDC)–mediated type I IFN production and the progression of SLE. Methods Metabolomic profiling of the serum from SLE patients and healthy controls was performed by mass spectrometry. The effects of SLE‐related metabolites on type I IFN production were explored in human and mouse pDCs. The reactive oxygen species (ROS) levels of pDCs from wild‐type and Ncf1 −/− mice were measured by flow cytometry. Mechanisms were investigated by RNA sequencing and immunoblotting. In vivo effects of SLE‐relevant metabolites were systemically analyzed in B6.Cg‐Sle1 NZM2410/Aeg Yaa/DcrJ mice. Results Taurine was higher in the serum from SLE patients compared to healthy controls ( P < 0.001) and rheumatoid arthritis patients ( P < 0.001). Taurine content was positively correlated with disease activity and the expression of IFN signature genes. The addition of taurine facilitated IFN regulatory factor 7 phosphorylation and enhanced type I IFN production by reducing the ROS levels in pDCs in a neutrophil cytosolic factor 1–dependent manner. Taurine supplementation promoted expression of type I IFN–induced genes, activated lymphocytes, and increased autoantibodies and proteinuria, leading to more serious nephritis. Conclusion Taurine metabolism is involved in the development of SLE by enhancing pDC‐mediated type I IFN production. Targeted inhibition of taurine or implementation of a taurine‐restricted diet has therapeutic potential in SLE.