Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients

Abstract

G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4⁺, CD8⁺, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19⁺CD27^-, CD19⁺CD27⁺, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27^-IgD⁺ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

Keywords:

• GPR183
• EBI2
• systemic lupus erythematosus
• ROC curve analysis
• Type I interferon

Author contributions

Haijing Wu devised the study and wrote this paper. Mingming Zhao performed flow cytometry on human samples and organised data statistics and graphs. Ming Yang analysed data, performed cell separation and mRNA expression analysis, and wrote the methods of the paper. Yang Mei carried out experiments and collected samples and clinical data. Zhidan Zhao, Pengpeng Cao and Yue Xin collected and analysed clinical data. Yunkai Guo provided clinical data and tonsil samples.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No.81773332, No.81972943), Hunan Talent Young Investigator (No. 2019RS2012) and Hunan Outstanding Young Investigator (No. 2020JJ2055).