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.

Effect of Resveratrol Dry Suspension on Immune Function of Piglets

“…The effect of resveratrol increasing the ratio of CD3+CD4+/CD3+CD8+ was confirmed in the obese model of C57BL/6 mice [ 20 ]. The reduction in CD3+CD4+/CD3+CD8+ ratio was usually associated with malignancies or the attack of the virus such as HIV infection [ 21 ], and the reduction also existed in the mouse model of systemic lupus erythematosus [ 22 ]. In our study, there was no significant difference between the normal and treated groups.…”

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

“…Similarly, lower levels of vitamin D caused a significant reduction ( p = 0.015) in the percentage of migrated Treg cells (CD4 + CD25 + CCR4 + ) compared with that of healthy controls ( 159 ). The CD4 + /CD8 + ratio was significantly higher ( p < 0.001) in patients with severe vitamin D deficiency compared with a vitamin D-insufficient group ( 149 ), and vitamin D supplementation elevated CD4 + CD8 + double-positive T cells ( 160 ) or inhibited the activation of CD4 + T cells ( Figure 2 ) through inhibition of the PKCδ/ERK pathway and reduced expression of inflammatory factors ( 161 ). Through vitamin D supplementation for 6 months in patients with SLE ( n = 20), hypovitaminosis D, Treg-cell balance (increased Treg cells and decreased effector Th1 and Th17 cells) and B-cell homeostasis were restored with reduced anti-dsDNA antibodies ( 162 ).…”

Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases

“…To assess this hypothesis, in vivo studies have used experimental models of autoimmune encephalomyelitis [ 24 ] and SLE. [ 25 , 26 ] Despite confirming the induction of regulatory T lymphocyte and double-positive CD4+/CD8+ T lymphocytes, [ 25 ] besides the inhibition of Th9 and Th17 lymphocytes by vitamin D, these studies still do not verify the clinical benefits of vitamin D supplementation as a treatment of autoimmune diseases. [ 3 ]…”