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Updated: Apr 6, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Uncovering Mediating Mechanisms Linking Immune Cells to Systemic Lupus Erythematosus: Insights into Mendelian
Zenghui Liu1,2, Lu Kuang1, Jiaxing Zhao1,2
1Department of Clinical Laboratory, the Affiliated Guangzhou Twelfth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Introduction:
Systemic lupus erythematosus (SLE) involves dysregulated immune cell function, though its exact pathogenic mechanisms remain unclear.
Methods:
We performed a two-sample Mendelian randomization (MR) study using extensive GWAS summary statistics, covering 731 immune cell phenotypes, 91 inflammatory proteins, 179 lipid types, 1,400 blood metabolites, and SLE cases. The analysis aimed to evaluate causal associations between these variables and SLE. Additionally, we investigated possible mediating roles of inflammatory proteins, blood lipids, and metabolites through mediation analysis, with various sensitivity tests confirming the reliability of our findings.
Results:
We identified 20 immune cell phenotypes, 3 inflammatory proteins, 3 lipid types, and 17 blood metabolites with significant causal associations with SLE. Mediation analysis revealed that the protective effect of CCR2 on CD62L+ myeloid DCs against SLE was partly mediated by phosphatidylcholine (O-18:1_20:4) (12%) and sterol ester (27:1/20:3) (10.4%). Moreover, sphingomyelin (d18:1/20:0, d16:1/22:0) accounted for 14.7% of the protective effect of CD28 on CD45RA- CD4+ cells, not Treg, against SLE.
Discussion:
These findings enhance our understanding of disease pathogenesis, indicating that modulating key metabolic pathways and immune regulatory nodes could represent promising therapeutic approaches. However, additional experimental studies are needed to validate these potential causal relationships.
Conclusion:
Using causal inference approaches, our study identifies immune cell-mediated mechanisms underlying SLE pathogenesis, involving inflammatory proteins, lipids, and metabolites. These findings suggest potential intervention pathways for further mechanistic exploration and therapeutic development.
