Dendritic cell-associated B7-H3 suppresses the production of autoantibodies and renal inflammation in a mouse model of systemic lupus erythematosus

• Published in: Cell death & disease 2019-05, Vol.10 (6), p.393-393, Article 393
• Main Authors: Zheng, Xu, Xiao, Ze Xiu, Hu, Li, Fang, Xuan, Luo, Liqun, Chen, Lieping
• Format: Article
• Language: English
• Subjects: 13/21; 13/31; 38/77; 631/250/251; 631/250/38; 64/60; 96/106; Animals; Antibodies; Antibodies - administration & dosage; Antibodies - immunology; Antibodies, Antinuclear - blood; Antibodies, Antinuclear - metabolism; Autoantibodies; Autoantibodies - blood; Autoantibodies - metabolism; Autoimmune diseases; B7 antigen; B7 Antigens - genetics; B7 Antigens - immunology; B7 Antigens - metabolism; Biochemistry; Biomedical and Life Sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; Cell Biology; Cell Culture; Dendritic cells; Dendritic Cells - metabolism; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA - immunology; Female; Fusion protein; Glomerulonephritis; Glomerulonephritis - etiology; Immunization; Immunology; Interleukin-6 - metabolism; Kidney - pathology; Kidneys; Life Sciences; Lupus; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - therapeutic use; Systemic lupus erythematosus
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1623-0

B7-H3 immune modulatory molecule has been implicated in the generation and pathogenesis of autoimmune diseases, the mechanism of action is less known. We explored the role of B7-H3 in the induction of autoantibodies and organ-directed inflammation in a murine systemic lupus erythematosus (SLE) model in which the immunization with DNA extracted from activated T cells induced the production of anti-DNA autoantibodies and subsequent glomerulonephritis, two hallmarks of human SLE. Mice deficient of B7-H3 or treated with a B7-H3 specific antibody produced significantly higher levels of anti-DNA autoantibodies and more severe glomerulonephritis than wild-type mice, indicating an inhibitory function of B7-H3 in this model. Interestingly, immunization of mice with DNA-pulsed dendritic cells induced severe SLE symptoms while B7-H3 on dendritic cells is required in this process. Importantly, treatment of mice with recombinant B7-H3Ig fusion protein effectively ameliorated progression of murine SLE, accompanied with decreased level of anti-DNA autoantibodies and alleviated glomerulonephritis, decreased autoantibody deposition and complement deposition in kidney. Our findings implicate a potential role of B7-H3 on dendritic cells in the induction of SLE and as a potential target for the treatment of autoimmune diseases.