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

Jun Li; Huihua Ding; Yao Meng; Guanhua Li; Qiong Fu; Qiang Guo; Zhihua Yin; Zhizhong Ye; Haibo Zhou; Nan Shen

doi:10.1002/art.41419

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

Arthritis Rheumatol. 2020 Dec;72(12):2106-2117. doi: 10.1002/art.41419. Epub 2020 Oct 25.

Authors

Jun Li¹, Huihua Ding¹, Yao Meng¹, Guanhua Li¹, Qiong Fu¹, Qiang Guo¹, Zhihua Yin², Zhizhong Ye², Haibo Zhou³, Nan Shen⁴

Affiliations

¹ Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
³ Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, and Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
⁴ Shanghai Institute of Rheumatology, State Key Laboratory of Oncogenes and Related Genes, and Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, and Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China, and Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, and University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.

PMID: 32608557
DOI: 10.1002/art.41419

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dendritic Cells / drug effects
Dendritic Cells / metabolism*
Dendritic Cells / pathology
Disease Progression
Female
Humans
Interferon Regulatory Factor-7 / metabolism
Lupus Erythematosus, Systemic / metabolism*
Lupus Erythematosus, Systemic / pathology
Male
Mice
Phosphorylation
Reactive Oxygen Species / metabolism
Rheumatic Fever / metabolism
Rheumatic Fever / pathology
Taurine / metabolism*
Taurine / pharmacology

Substances

Interferon Regulatory Factor-7
Reactive Oxygen Species
Taurine