Cells Driving Lupus Kidney Disease Identified by Researchers

Researchers at the Singapore Immunology Network at A*STAR have found that immune dendritic cells are crucial for the development of kidney disease in systemic lupus erythematosus (SLE).

The study, “RNA sensing by conventional dendritic cells is central to the development of lupus nephritis,” was published in the journal PNAS.

The research team at A*STAR, led by Anna-Marie Fairhurst, PhD, has been trying to figure out which immune cells contribute to the processes that lead to this feared complication of lupus, which affects about one-third of patients.

Researchers have known for some time that a protein called TLR7 (toll-like receptor 7) is involved in the process leading to kidney disease. Even mildly elevated levels trigger the development of kidney disease.

The protein is usually a part of the system recognizing microbes during an infection and mediates an immune attack on the kidneys in some lupus patients. However, the reason behind this is still not clear.

In an earlier study published in the The Journal of Immunology, the same team used mice engineered to have levels of TLR7 twice as high as normal mice, leading to kidney disease. When they removed the receptor from B-cells only, the condition progressed as usual, leading researchers to conclude that B-cells are not involved in the processes leading to kidney disease.

Now, the team removed TLR7 only from dendritic cells in mice, which completely prevented severe autoimmune tissue damage.

Further analyses showed that it was a specific subtype of dendritic cells that was responsible for the autoimmune tissue damage. But in humans, this cell type does not usually carry TLR7 receptors on its surface, so researchers had to consider if their findings were really relevant for human disease, or if the results were just valid in the mouse model.

As part of the immune defense against infections, an immune cell increases the amount of TLRs on its surface when it encounters a threat. So to test if human dendritic cells of the type identified in mice would increase TLR7 when encountering common infections, researchers isolated those specific cells from healthy people and grew them in the lab.

When cells encountered an influenza virus or IFN-alpha — a molecule stimulating immune reactions — they started carrying TLR7 on their surface.

“Our studies show that these cells switch mild autoimmune phenotypes to severe kidney disease,” said Fairhurst in a news release.

The team now plans to explore TLR7 in patients with lupus in an attempt to link the factor to various autoimmune symptoms.