Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with Sjogren's syndrome

被引:4
作者
Zhou, Ying-Bo [1 ]
Yuan, Xiang [1 ]
Wang, Qi-Kai [1 ]
Zhang, Hong [1 ]
Wang, Guo-Sheng [1 ]
Li, Xiang-Pei [1 ]
Wang, Yiping [2 ]
Harris, David [2 ]
Li, Xiao-Mei [1 ]
机构
[1] Univ Sci & Technol China, Dept Rheumatol & Immunol, Affiliated Hosp USTC 1, Div Life Sci & Med, Hefei 230001, Anhui, Peoples R China
[2] Univ Sydney, Westmead Inst Med Res, Westmead, NSW 2145, Australia
基金
中国国家自然科学基金;
关键词
CD40; Sjogren's syndrome; DNA vaccine; Salivary glands; Autoimmune; EPITHELIAL-CELLS; DENDRITIC CELLS; CLINICAL-TRIALS; EXPRESSION; LIGAND; ACTIVATION; MECHANISMS; STRATEGIES; NEPHRITIS; APOPTOSIS;
D O I
10.1016/j.imlet.2020.07.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Overexpression of CD40 has been reported in patients with primary Sjogren's syndrome (pSS). The increased CD40 expression promote autoimmune response and enhance inflammation in pSS. The aim of this study is to block CD40-CD154 interaction with CD40 DNA vaccine to slow the disease progression of SS in non-obese diabetic (NOD) mice. Methods: Female NOD mice were treated with CD40 DNA vaccine, empty vector and normal saline. The salivary flow rate was measured, whereas lymphocytes infiltration in the salivary glands was assessed by histopathology. Expression of CD40 and B220 in salivary were examined by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. CD40, IL-1 beta, TNF-alpha and IL-6 levels in the salivary glands were detected by PCR. Serum anti-CD40 antibody was measured by ELISA. Serum anti-nuclear antibody (ANA) was monitored by immunofluorescence. Results: NOD mice treated with CD40 DNA vaccine showed higher levels of anti-CD40 antibody compared with the controls. The expression of CD40 in the salivary glands of NOD mice in CD40 DNA vaccine group was decreased. The infiltration of lymphocytes was reduced in the salivary glands and saliva secretion was increased in the treatment group. The expression level of TNF-alpha and IL-6 in salivary glands were declined. The splenic dendritic cell and plasma cell populations were reduced and the level of ANA was decreased in NOD mice with CD40 DNA vaccine treatment. Conclusions: CD40 DNA vaccine inhibits the immune response and reduce inflammation in epithelial tissues SS in non-obese diabetic (NOD) mice, suggesting that CD40 DNA vaccine could be a new therapeutic approach in treatment of pSS.
引用
收藏
页码:62 / 70
页数:9
相关论文
共 51 条
[1]  
[Anonymous], 2019, SCI TRANSL MED
[2]  
[Anonymous], 2019, CLIN EXP RHEUMA S118
[3]  
[Anonymous], 2019, CLIN EXP RHEUMA S118
[4]  
[Anonymous], 2017, ISR MED ASSOC J
[5]   The CD40-CD154 interaction in B cell-T cell liaisons [J].
Bishop, GA ;
Hostager, BS .
CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (3-4) :297-309
[6]  
Brignole F, 2000, INVEST OPHTH VIS SCI, V41, P1356
[7]   Sjogren syndrome [J].
Brito-Zeron, Pilar ;
Baldini, Chiara ;
Bootsma, Hendrika ;
Bowman, Simon J. ;
Jonsson, Roland ;
Mariette, Xavier ;
Sivils, Kathy ;
Theander, Elke ;
Tzioufas, Athanasios ;
Ramos-Casals, Manuel .
NATURE REVIEWS DISEASE PRIMERS, 2016, 2
[8]   Light-Emitting Diode at 460 ± 20 nm Increases the Production of IL-12 and IL-6 in Murine Dendritic Cells [J].
Carvalho-Costa, Tamires Marielem ;
Mendes, Maria Tays ;
da Silva, Marcos Vinicius ;
Rodrigues, Virmondes, Jr. ;
Marre Bruschi Thedei, Giuliana Cristina ;
Freire Oliveira, Carlo Jose ;
Thedei, Geraldo, Jr. .
PHOTOMEDICINE AND LASER SURGERY, 2017, 35 (10) :560-566
[9]   Progress in understanding autolmmune exocrinopathy using then on-obese diabetic mouse: An update [J].
Cha, S ;
Peck, AB ;
Humphreys-Beher, MG .
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE, 2002, 13 (01) :5-16
[10]  
Daniels T.E., 2011, ARTHRITIS RHEUM, V63