Low Level of Vitamin D Increased Dendritic Cell Maturation and Expression of Interferon-γ and Interleukin-4 in Systemic Lupus Erythematosus

Abstract

Vitamin D has been reported contribute to the regulation of immune responses by inhibiting DC maturation, T cell-dependent DC activation, reduce the secretion of Th1 and Th2 cytokines and induce the development of regulatory T cells. The aimed of this study to determine the association of vitamin D level with DC maturation, IFN-γ and IL-4 cytokine expression in Indonesian SLE patients.The study was conducted in fifty four active disease SLE patients (SLEDAI score>5 p = 0.433). Vitamin D (1,25(OH)2D3) serum concentration was significantly lower in Indonesian SLE patients compared with healthy controls. The low concentration was related to higher expression of CD11c+/CD86/CD40/CD83 in iDC cells and higher secretion of Th1 cytokines (IFN-γ) and Th2 cytokines (IL-4). Keywords: vitamin D, CD11c+/CD86/CD40/CD83, IFN-γ, IL-4, SLE I. BackgroundSystemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that occurs more frequently in the last decade. The etiology and pathogenesis of SLE remains unclear, however evidences suggest that deviation function of T cells, B cells, monocytes and regulatory T cells ultimately lead to systemic inflammation and tissue damages [1,2]. Although the 10-year life expectancy of SLE patients has risen significantly to 90% in developed countries, a study by Handono showed that life expectancy of SLE patients in Indonesia remains low, 70% within 5-year and 55% with in 10-year [3].A recent study concluded an association between the onset of autoimmune disease with vitamin D deficiency [4]. A high percentage of these patients have been found to live in continental/temperate climate countries [5]. Vitamin D contributes to the regulation of immune responses in several ways by inhibiting monocyte differentiation into dendritic cells (DC), inhibiting DC maturation or differentiation, and maintaining the condition of immature DC (iDC) [6]. Furthermore, it has been reported that vitamin D inhibits the activation of T cell-dependent DC [7], reduces the secretion of Th1 and Th2 cytokines and induces the development of regulatory T cells (Treg) [8].It has been known that DC maturation markers are surface molecular expression of CD11c+/CD86/CD40/CD83. Monocytes (moDC) that develope into DC are characterized by the expression of CD11c+ and lower expression of CD86/CD40/CD83 co-stimulatory molecules. However, expression of the molecules will increase in immature DC (iDC) and the highest expression occurred in mature DC (mDC).