Abstract
Behcet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic and recurrent autoimmune diseases associated with abnormal T cell immune response. Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) have been reported to be involved in T cell mediated autoimmune disease. This study aimed to investigate the role of C3aR and C5aR in these two diseases. The C3aR expression in PBMCs was increased in patients with active BD (aBD) and active VKH (aVKH). No statistical difference was found concerning the expression of C5aR in PBMCs between patients with aBD or aVKH and normal controls. After the intraocular inflammation in BD and VKH patients was controlled, the C3aR expression returned back to normal levels. The serum from patients with aBD and aVKH significantly induced C3aR expression by PBMCs. C3a induced IL-6, IL-1β and TNF-α secretion, while inhibited the production of IL-10 by monocytes. Activation of C3aR in CD4+T cells could upregulate IL-17 production and inhibit IL-10 production, but had no detectable influence on IFN-γ production. Our data indicates that increased C3aR expression may lead to over activation of the Th17 cell response and may therefore contribute to the pathogenesis of BD and VKH disease.
Highlights
Uveitis is the third leading cause of preventable vision loss worldwide[1]
We examined the expression of Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) in idiopathic active acute uveitis (AAU) which served as a disease control group
Our study showed that patients with active BD (aBD) or active VKH (aVKH) had an increased expression of C3aR, but not C5aR, in their PBMCs compared to healthy controls
Summary
Uveitis is the third leading cause of preventable vision loss worldwide[1]. There are two most common uveitis entities in China which are known as Behcet’s disease (BD) and Vogt- Koyanagi-Harada (VKH) disease[2]. Previous studies demonstrated that locally produced C3a and C5a interacting with their receptor on APCs and T cells are involved in T cell differentiation[9] Recent studies in both mice and humans have shown that C3a and C5a participated in regulating T cell responses by modulating dendritic cell (DC) function[10,11]. Recent studies suggest that C3aR and C5aR participated in the development of experimental autoimmune uveitis(EAU), as evidenced by a marked reduction in the severity of inflammation and decreased pathogenic T cell responses in C3aR/C5aR-deficient mice[14]. These studies indicate that C3aR/C5aR signaling is important for the development www.nature.com/scientificreports/. The serum from active BD and VKH disease could induce the upregulation of C3aR in PBMCs, and the activation of C3aR could induce Th17-polarizing cytokines by monocytes and IL-17 production by CD4+T cells
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