OBJECTIVE

The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of and sphingosine-1-phosphate receptor 1 () in the pathogenesis of systemic lupus erythematosus.

METHODS

We analyzed miRNA and mRNA profiling data of CD4 splenic T cells derived from MRL/MpJ- /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6- mice and the lupus phenotypes were analyzed.

RESULTS

In CD4 splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, by RNA sequencing of MRL/MpJ- /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of . The mRNA levels of were significantly decreased after miR-223-3p overexpression. In B6- mice, the proportion of CD3 T cells, CD3CD4CD8 cells, B cells, plasma cells, and S1PR1CD4 T cells in the spleen was significantly increased compared with that in B6- mice by flow cytometry. B6- mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1CD4 T cells.

CONCLUSION

Unexpectedly, the deletion of exacerbated the lupus phenotypes associated with increased population of S1PR1CD4 T in spleen and the enhanced infiltration of S1PR1CD4 T cells in inflamed kidney tissues, suggesting compensatory role of in the pathogenesis of lupus nephritis.