Effects of 1,25(OH)2D3 and vitamin D receptor on peripheral CD4+/CD8+ double-positive T lymphocytes in a mouse model of systemic lupus erythematosus

Abstract

This study aims to explore effects of 1,25(OH)2D3 and vitamin D receptor (VDR) on peripheral CD4+/CD8+ double-positive (DP) T lymphocytes in systemic lupus erythematosus (SLE). MRL-LPr/LPr mice with SLE (n = 20) and normal MRL mice (n = 20) were assigned into the control group (normal mice, without feeding with 1,25(OH)2D3), the 1,25(OH)2D3 group (SLE mice, feeding with 1,25(OH)2D3), the VDR-knock-in + 1,25(OH)2D3 group (SLE mice, VDR-knock-in, feeding with 1,25(OH)2D3) and the VDR-knockout group (normal mice, VDR-knockout, without feeding with 1,25(OH)2D3) (n = 10 per group). Levels of T lymphocytes were measured by flow cytometry. The mRNA and proteins expressions of inflammatory factors were measured by qRT-PCR and ELISA. Extracellular signal-regulated kinase-1/2 (ERK1/2) expression was measured by Western blotting. Compared with normal mice, SLE mice showed reduced levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes. The levels of SLE-related indicators all increased significantly, followed with severe skin ulcers and urinary system infection. With the increase in time, skin ulcers and urinary system infection were significantly improved, levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes increased, and levels of SLE-related indicators all decreased in the 1,25(OH)2D3 group. There were no significant changes in bioindicators in the control and the VDR-knock-in + 1,25(OH)2D3 groups. The symptoms of SLE gradually occurred in the VDR-knockout group. This study demonstrates that VDR and 1,25(OH)2D3 could elevate CD4+/CD8+ DP T lymphocytes and reduce expressions of inflammatory factors, thus inhibiting the development and progression of SLE.