Researchers at Pohang University of Science and Technology (POSTECH) have identified a protein that plays a role in the development of the autoimmune disease lupus. The study, led by Professor Yoontae Lee and PhD candidate Jiho Park from the Department of Life Sciences, was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
B cells are part of the immune system and produce antibodies to fight off invading pathogens like viruses. T follicular helper (TFH) cells support B cells in producing antibodies. When there is an excess of TFHs, B cells can become overactive, leading to autoimmune diseases. In these conditions, B cells mistakenly target the body’s own tissues and cells, producing autoantibodies even in the absence of external threats.
Lupus, a common autoimmune disease, is characterized by a distinctive red rash on the face and joint pain, especially in the nose and cheeks. The symptoms and immune cells affected can vary among patients, making personalized treatment challenging due to the unclear understanding of the disease’s cause and mechanisms.
Prior research by Professor Yoontae Lee’s team indicated that a transcription factor called ETV5, expressed in T cells, promotes the formation of TFH cells, potentially contributing to lupus. In their recent study, the team conducted experiments on both mice and humans to validate this hypothesis.
The researchers found that by reducing ETV5 in a mouse model of lupus, they could decrease autoimmune symptoms such as abnormal antibody levels, immune cell infiltration in body tissues, kidney inflammation, and the production of TFH cells. They discovered that ETV5 boosts the expression of a protein called osteopontin (OPN), which then activates AKT protein, leading to the differentiation of TFH cells.
Moreover, the team confirmed that the levels of ETV5 and OPN expression also influence the differentiation of TFH cells in human T cells. Consistent with the animal studies, SLE patients showed higher levels of ETV5 and OPN compared to the general population. Additionally, disease severity and autoantibody levels correlated with the levels of ETV5 and OPN expression.
Professor Yoontae Lee, the lead researcher, highlighted the significance of their findings, stating, “Our experiments have unveiled a mechanism of lupus development involving ETV5 and OPN.” He expressed hope that future studies could lead to the creation of ETV5 inhibitors to regulate TFH cell development and assist in treating lupus patients.
The study received support from the Mid-Career Research Program of the Ministry of Science and ICT.
