Vitamin D3 Alters the Expression of Toll‐like Receptors in Peripheral Blood Mononuclear Cells of Patients With Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self-nucleic acids by intracellular Toll-like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti-inflammatory and immunomodulatory effects of 1,25-dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention. The present study investigated the effects of vitamin D3 on the expression of TLR3, TLR7, and TLR9 in SLE patients. Study participants included 20 SLE patients and 20 age- and sex-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured in the presence or absence of vitamin D3 (50 nM). Then RNA was extracted, cDNA was synthesized and gene expression levels of TLR3, TLR7, and TLR9 were assessed using real-time PCR. Up-regulated expression levels of TLR7 and TLR9 were observed in the PBMCs of SLE patients in comparison with controls. Culturing PBMCs with vitamin D3 significantly down-regulated the expression of TLR3 (8.86 ± 4.2 for SLE patients vs. 45.34 ± 18.6 for control; P = 0.03), TLR7 (17.91 ± 7.7 for SLE patients vs. 242.37 ± 89.6 for controls; P = 0.0001) and TLR9 (4.67 ± 1.9 for SLE patients vs. 8.9 ± 1.5 for controls; P = 0.007) in SLE patients in comparison with healthy controls. The results of the current study suggest that vitamin D3 could exert some of its immunomodulatory effects in SLE patients via affecting the expression levels of some TLRs. J. Cell. Biochem. 118: 4831-4835, 2017. © 2017 Wiley Periodicals, Inc.

Serum hepcidin and interleukin-6 in systemic lupus erythematosus patients: crucial factors for correction of anemia

“…Systemic lupus erythematosus is a potentially severe autoimmune disease with characteristic production of inflammatory cytokines and autoreactive antibodies due to the lack of immune tolerance leading to diverse clinical manifestations and damage to various organs, including skin, joints, kidneys, and the central nervous system [13]. SLE course is variable, mainly characterized by remission and relapse periods [14].…”

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

“…Increased levels of antinuclear antibodies, IL-23, and IL-17 (important for Th17 development and function) were also significantly associated ( p < 0.05) with a vitamin D deficiency ( 120 ). Abnormal activation of toll-like receptors (TLRs) contributes to the pathogenesis of SLE, and, interestingly, vitamin D exerts some of its immunomodulatory effects in patients with SLE by significantly downregulating the expression levels of TLR3 ( p = 0.03), TLR7 ( p = 0.0001), and TLR9 ( p = 0.007) ( 150 ). Autoimmune diseases like SLE may result from a conversion of Treg cells into Th17 cells, and in the serum of patients with SLE, IL-17 levels were abnormally high.…”

The immunomodulatory role of probiotics in allergy therapy

“…The stimulation by TLR was said to have a mechanistical effect on innate immunity that could increase differentiation of the Th1 cell, maintain an anti-inflammatory state, and induce modulatory cytokine such as IL-10 and TGF-β, along with an increased level of intestinal IgA (Gourbeyre, Denery, & Bodinier, 2011;Marschan et al, 2008). Many studies showed that probiotics promote the stimulation of uptake receptors on blood polymorphonuclear leukocytes, and can induce higher expression of TLRs and complement receptor 3 (CR3), which are involved in a phagocytic capacity (Fang, Elina, Heikki, & Seppo, 2000;Niers et al, 2005;Pagnini et al, 2010;Yazdanpanah et al, 2017). The lactobacilli strain in different doses showed that it can enhance or suppress T cell immune responses (Wen et al, 2012).…”