New research found that a specific set of immune cells named plasmacytoid dendritic cells (pDCs), long believed to cause lupus disease, actually did not contribute to late-stage lupus in a mice model. The paper, which has potential implications for future disease treatment, was published in The Journal of Immunology and is titled “Cutting Edge: Plasmacytoid Dendritic Cells in Late-Stage Lupus Mice Defective in Producing IFN-α.“
Lupus is an inflammatory condition in which the immune system attacks healthy cells, resulting in painful joints, fever, chronic fatigue, and, eventually, renal failure. It is believed that the disease results from genetic abnormalities, and early research revealed it to be linked to a protein secreted by pDCs called interferon alpha. This link was confirmed by cancer patients receiving interferon alpha, who frequently developed lupus symptoms. Subsequent studies found that removing pDC cells ameliorated lupus symptoms in mice models of the disease.
Now, new research suggests that symptom reduction depends on the stage of the disease. “When the researchers removed the cell type early in the disease, they found that it was really strong at disease attenuation. But in studying this phenomenon further, we found in our experiments that for some reason mice with late-stage lupus didn’t produce interferon alpha at all. We asked ourselves, ‘How can these cells be pathogenic if they are not producing this pathogenic protein?” the study’s lead author, Dr. Xin M. Luo, explained in a press release.
In this study, the team used novel cell-sorting technology to isolate high purity pDCs from mice bone marrow. The cells were then studied by means of RNA sequencing and the resulting data analyzed, suggesting that pDCs do not contribute to lupus development if the disease has already started, but could be a factor before its onset. “We answered the question that people have been wondering for many years: do these cells actually contribute to disease? Our data strongly suggests that, in patients who already have lupus, pDCs don’t contribute to disease anymore. The damage is already done,” Dr. Luo said.
“We believe that these cells are only involved in the initiation of lupus, not the later exacerbation or progression of the disease,” he added. “This is very clinically relevant because many researchers are still thinking about targeting pDCs as a treatment for lupus patients, which may not work.”
Importantly, the team also discovered that this technology could be used to identify lupus biomarkers at early stages of disease development. “We can move forward with this set of data to investigate possible early detection and figure out the role of the altered pDCs on lupus. It’s too early to know how these changes are going to affect treatment, but these are the building blocks,” concluded Dr. S. Ansar Ahmed, head of the Department of Biomedical Sciences and Pathobiology and study co-author.