Inhibition of CD83 Alleviates Systemic Inflammation in Herpes Simplex Virus Type 1-Induced Behçet’s Disease Model Mouse

Abstract

Behçet’s disease (BD) is an autoinflammatory disease that can lead to life- and sight-threating complications. Dendritic cells (DCs) are the most potent antigen-presenting cells that can regulate multiple inflammatory pathways. The objective of this study was to investigate the association of the DC stimulatory molecule CD83 with BD. Frequencies of costimulatory molecules expressing DCs in peripheral blood leukocytes (PBL) were measured by flow cytometry (FACS). The severity of symptoms in HSV-1-induced BD symptomatic mice was also assessed. Frequencies of CD83-positive cells were significantly increased in mice exhibiting BD symptoms, compared to those in asymptomatic mice. Abatacept, a CD80/86 blocker, significantly decreased the frequencies of CD83-positive cells in a time- and dose-dependent manner. BD symptomatic mice treated with Abatacept showed gradual reduction in the severity score of symptoms. Intraperitoneal injection of CD83 siRNA significantly reduced the frequencies of CD83-positive cells in PBL and peritoneal macrophages. After CD83 siRNA injection, BD symptoms of mice were improved and disease severity was decreased. Discontinuation of CD83 siRNA deteriorated symptoms while readministration of CD83 siRNA again improved BD symptoms of mice. These results clearly indicate the involvement of CD83-expressing cells in the inflammatory symptoms of BD. Therefore, CD83 might be useful as a therapeutic target for BD.

Interrelationship of Stress, Environment, and Herpes Simplex Virus Type-1 on Behçet’s Disease: Using a Mouse Model

“…Inhibition of CD83 could significantly prevent DC-mediated T cell activation (25,58). In our previous reports, inhibition of CD83, with CD83 siRNA, was able to improve BD symptoms in mice (24). In the current study, noise stress treated BD mice improved when CD83 was suppressed.…”

“…As a control group, mice were treated with PBS for the same period. CD83 siRNA was prepared as previously described ( 24 ). CD83 siRNA was mixed with a transfection reagent JetPEI (Polyplus-transfection, Illkirch-Graffenstaden, France) for injection into mice.…”

“…Preparation of siRNA CD83 siRNA preparation was performed as detailed previously (24). In brief, CD83 siRNA oligonucleotides with the following sense and antisense sequences were synthesized by Integrated DNA Technology (Coralville, IA, USA): Sense, 5'-GUGCUUUUCAGUCAUCUACAAGCTA-3'; Antisense, 3'-CUCACGAAAAGUCAGUAGAUGUUCGAU-5'.…”

“…CD40, CD80, CD83, and CD86 are DC costimulatory molecules ( 23 ). Among them, CD83 is known to play a pathogenic role in BD mice ( 24 ). It has been reported that inhibition of CD83 by GC7 can affect the ability of DCs to induce T cell proliferation ( 25 ).…”

Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83

“…The downregulation of CD83 through RNA interference in human DC results in the less potent induction of allogeneic T cell proliferation and decreases interferon (IFN)-γ secretion ( 21 ). CD83 inhibition by CD83 siRNA was reported to improve the symptoms of BD mice ( 26 ).…”