Crucial role of dendritic cells in a fatal renal condition of Lupus (SLE) revealed by A*STAR researchers
Systemic lupus erythematosus (SLE), simply known as lupus, is an autoimmune disease, where the body’s immune system mistakenly attacks its own healthy tissues in many parts of the body. The symptoms of this disease include joint pain, heart inflammation and a butterfly-shaped rash across the nose and cheeks. These can sometimes worsen and result in life-threatening kidney disease.
A team of researchers at A*STAR Singapore immunology Network led by Dr. Anna-Marie Fairhurst have been working on finding the exact pathological origin of kidney disease in SLE patients. Normal immune cells of healthy individuals are known to express a protein called Toll-like receptor 7 (TLR7). This protein helps the immune cells in recognizing foreign pathogens. However, it was observed that in mice suffering from SLE, high expression of TLR7 leads to the death of kidney cells.
Previously, Dr. Fairhurst and her team have eliminated the role of B cells in this condition and have since, moved on to the antigen-presenting dendritic cells.
The study carried out in A*STAR, involved the hyper expression (double) of TLR7 in mouse model of SLE and subsequently, selectively eliminating the surplus receptors from individual immune cell populations.
While, upon deletion of TLR7 of B cells, the disease continued to progress, the deletion of TLR7 in dendritic cells, caused the disease to stop and kidney inflammation was absent. Upon analysing further, it was found that a specific type of dendritic cell, known as conventional CD11b+ was the one responsible for infiltrating the kidneys and causing the disease.
While the studies revealed the cause of autoimmune kidney disease in mice, the human diseased dendritic cells were not found to express TLR7. In order to further understand this, the team isolated dendritic cells from blood samples of healthy human individuals and modified them into expressing TLR7 using heat inactivated or live flu viruses or interferon-alpha (type of immune response protein).
The live influenza virus and interferon-alpha were able to increase the TLR7 expression in human dendritic cells.
In continuation with these findings, Dr. Fairhurst and her team plan to carry out an analysis of the blood samples from human patients of SLE and chart the TLR7 expression levels for the different manifestations of autoimmunity. SLE patients are commonly prescribed annual flu vaccinations, however, Dr. Fairhurst wishes to investigate the various vaccination strategies that could be beneficial to SLE patients.
Dr. Fairhurst said, “More than two-thirds of SLE patients ‘in remission’ still suffer and take daily medication. We hope to make some changes in this process.”