Altered microRNAs expression in T cells of patients with SLE involved in the lack of vitamin D

Vitamin D has been recognized as a potent immunomodulator and its deficiency is common in different population groups including patients with SLE. As miRNAs regulation plays a significant role in SLE, the present study aimed to evaluate the association between vitamin D status and miRNAs levels in patients with SLE. The serum concentrations of vitamin D (25-hydroxyvitamin D) and the levels of six miRNAs in T cells from patients with SLE were measured in 42 SLE cases and 48 healthy controls. Vitamin D treatment was also performed in isolated and cultured T cells from SLE patients in different times and doses. Vitamin D insufficiency (25-hydroxyvitamin D concentration<20 ng/ml) was more common in cases than in controls. Although age and BMI were similar, cases had significantly lower concentrations of miRNA-377, miRNA-342, miRNA-10a, miRNA-374b, miRNA-125a, and miRNA-410 than controls. Furthermore, a significant positive correlation was also observed between 25-hydroxyvitamin D concentrations and measured miRNAs levels. A significant difference in observed miRNAs levels was also observed in patients with 25-hydroxyvitamin D insufficiency compared with patients with 25-hydroxyvitamin D concentration≥20 ng/ml. And 1α,25(OH)2D3 differentially regulated miRNAs expression in dose- and time- manner in vitro. Lower expressions of miRNA-377, miRNA-342, miRNA-10a, miRNA-374b, miRNA-125a, and miRNA-410 were found in SLE patients. And severe vitamin D deficiency is associated with decreased observed miRNAs levels in SLE patients. A 25-hydroxyvitamin D concentration value<20 ng/ml is suggested as the "cut-off" for such immunological alterations in patients with SLE.

[1]  W. März,et al.  Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study , 2017, European Journal of Nutrition.

[2]  G. Murugaiyan,et al.  Contribution of MicroRNAs to autoimmune diseases , 2016, Cellular and Molecular Life Sciences.

[3]  J. Harley,et al.  Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification , 2016, Annals of the rheumatic diseases.

[4]  H. Berendse,et al.  Systematic Review of the Relationship between Vitamin D and Parkinson’s Disease , 2016, Journal of Parkinson's disease.

[5]  S. Surman,et al.  Vitamin Supplementation at the Time of Immunization with a Cold-Adapted Influenza Virus Vaccine Corrects Poor Mucosal Antibody Responses in Mice Deficient for Vitamins A and D , 2016, Clinical and Vaccine Immunology.

[6]  C. Xiao,et al.  The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity , 2015, Nature Immunology.

[7]  D. Trump,et al.  Vitamin D Signaling Modulators in Cancer Therapy. , 2016, Vitamins and hormones.

[8]  A. Marette,et al.  Vitamin D reduces LPS-induced cytokine release in omental adipose tissue of women but not men , 2015, Steroids.

[9]  M. Iruretagoyena,et al.  Immune Response Modulation by Vitamin D: Role in Systemic Lupus Erythematosus , 2015, Front. Immunol..

[10]  J. Oates,et al.  A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial Function in Lupus Patients , 2015, The American journal of the medical sciences.

[11]  S. Fouzas,et al.  Vitamin D and Cystic Fibrosis Lung Disease. , 2015, Mini reviews in medicinal chemistry.

[12]  R. Bak,et al.  Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus , 2015, Arthritis Research & Therapy.

[13]  K. Ansel,et al.  MicroRNA regulation of lymphocyte tolerance and autoimmunity. , 2015, The Journal of clinical investigation.

[14]  Vaishali R. Moulton,et al.  T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity. , 2015, The Journal of clinical investigation.

[15]  Yue Zhang,et al.  Decreased expression of microRNA-125a-3p upregulates interleukin-23 receptor in patients with Hashimoto’s thyroiditis , 2015, Immunologic research.

[16]  F. Dall’ara,et al.  A 24-month prospective study on the efficacy and safety of two different monthly regimens of vitamin D supplementation in pre-menopausal women with systemic lupus erythematosus , 2015, Lupus.

[17]  F. Dall’ara,et al.  Phenotype modifications of T-cells and their shift toward a Th2 response in patients with systemic lupus erythematosus supplemented with different monthly regimens of vitamin D , 2015, Lupus.

[18]  Martin Healy,et al.  An Association between MicroRNA-21 Expression and Vitamin D Deficiency in Coronary Artery Disease. , 2015, MicroRNA.

[19]  T. Chan,et al.  The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus , 2015, Clinical Epigenetics.

[20]  E. Morand,et al.  Vitamin D and systemic lupus erythematosus: continued evolution , 2015, International journal of rheumatic diseases.

[21]  P. Heegaard,et al.  Circulating Extracellular microRNA in Systemic Autoimmunity. , 2015, Experientia supplementum.

[22]  Wen-jie Fan,et al.  microRNA-126 expression and its mechanism of action in patients with systemic lupus erythematosus. , 2015, European review for medical and pharmacological sciences.

[23]  Honglong Wu,et al.  DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype. , 2014, Journal of autoimmunity.

[24]  Y. Li,et al.  MicroRNA-mediated mechanism of vitamin D regulation of innate immune response , 2014, The Journal of Steroid Biochemistry and Molecular Biology.

[25]  F. Wang,et al.  The Regulatory Roles of MicroRNA-146b-5p and Its Target Platelet-derived Growth Factor Receptor α (PDGFRA) in Erythropoiesis and Megakaryocytopoiesis* , 2014, The Journal of Biological Chemistry.

[26]  M. Cutolo,et al.  Vitamin D, steroid hormones, and autoimmunity , 2014, Annals of the New York Academy of Sciences.

[27]  T. Bíró,et al.  The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes, but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients , 2014, Rheumatology International.

[28]  M. Cutolo.  Further emergent evidence for the vitamin D endocrine system involvement in autoimmune rheumatic disease risk and prognosis , 2013, Annals of the rheumatic diseases.

[29]  M. Cutolo,et al.  1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokines in human macrophages. , 2012, Clinical and experimental rheumatology.

[30]  L. Nguyễn,et al.  The beneficial role of vitamin D in systemic lupus erythematosus (SLE) , 2012, Clinical Rheumatology.

[31]  Gang Wang,et al.  Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus , 2012, Clinical Rheumatology.

[32]  Lauren L. Ritterhouse,et al.  B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels. , 2011, Arthritis and rheumatism.

[33]  P. Lipsky,et al.  Mechanisms of B cell autoimmunity in SLE , 2011, Arthritis research & therapy.

[34]  G. Tsokos,et al.  T cells as therapeutic targets in SLE , 2010, Nature Reviews Rheumatology.

[35]  C. Marques,et al.  The importance of vitamin D levels in autoimmune diseases. , 2010, Revista brasileira de reumatologia.

[36]  Kaleb M. Pauley,et al.  MicroRNA in autoimmunity and autoimmune diseases. , 2009, Journal of autoimmunity.

[37]  P. Lipsky,et al.  Modulatory Effects of 1,25-Dihydroxyvitamin D3 on Human B Cell Differentiation , 2007, The Journal of Immunology.

[38]  H. Cook,et al.  Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus , 2006, Nature Clinical Practice Rheumatology.

[39]  P. Lips.  Which circulating level of 25-hydroxyvitamin D is appropriate? , 2004, The Journal of Steroid Biochemistry and Molecular Biology.