In a research report published in the international journal Proceedings of the National Academy of Sciences, scientists from institutions such as the Caroline Academy in Sweden revealed how special lymphocyte populations can abandon their regulation in the immune system through research Role to promote the occurrence of autoimmune diseases, relevant research results may provide new ideas and direction for scientists to develop new treatments for autoimmune diseases.
Autoimmune diseases are the result of the imbalance of the body's immune system, which induces the destruction and interference of various mechanisms that normally inhibit the occurrence of diseases. Now researchers have discovered that the cell population that normally was blocked autoimmunity may transform its function into promoting disease, which may be the result of inflammation and a specific stimulation combination of glycolipids.
Studies have shown that the lymphocyte population called iNKT cells normally inhibits autoreactive B cells from secreting pathogenic antibodies, but now it will lose this ability, instead, playing a key role in promoting B cells which will cause neutrophils to lose their function. It normally regulates its own function and enhances the severity of rheumatoid arthritis in disease models.
When using glycolipid agonist α-galactosylceramide (aGalCer) and inflammatory cytokine IL-18 to stimulate iNKT cells, the researchers identified a special switch from iNKT cells. iNKT cells will exhibit lower levels of increased transcription factor GATA3 and transcription factor BCL6 levels, while also increasing the expression levels of CXCR5 and PD-1 (a typical follicular helper T cell phenotype) on the cell surface.
In this research, the researchers used a special reporting system in which B cells undergoing germinal center reactions upregulate human-specific markers. They clarified that combining glycolipids with iNKT cell inflammatory stimuli in the body may be able to make more B cells undergo GC reaction. Under normal circumstances, regulatory iNKT cells can interact with neutrophils to regulate the function of B cells, but the researchers found that this interaction may disappear during the function conversion process. Therefore, in order to verify whether this switch in iNKT cells can be sufficient to drive the development of autoimmunity, the researchers used a collagen-induced arthritis model to process the research, co-administration of aGalCer and IL-18 may lead to early rheumatoid arthritis and increased immune cell activation.
The research results reveal the mechanism of autoimmune diseases and how the safety mechanism of the immune system is disturbed. In addition, related research results can also help researchers develop new strategies to restore the balance of the body's immune system to treat a variety of autoimmune diseases.