The body’s immune response is a balanced behavior. Excessive amounts can lead to inflammation or autoimmune diseases. Too little can lead to serious infections. Regulatory T cells, or Tregs, are important to maintain this balance. It plays a role of "brake" in the immune response process of the body to avoid excessive immune response. Therefore, controlling the number and activity of Tregs is particularly important for maintaining the health of the body. Recently, in a research report published in the international Journal of Clinical Investigation, scientists from the University of Pennsylvania and other institutions have found that the molecule named DEL-1 can be used as an effective method to help treat inflammation or suppress autoimmune response by targeting. DEL-1 molecule can promote the production of Tregs and its immunosuppressive activity.
Researcher Hajishengallis said that in the early studies, we found an association, that is, during the period of inflammation subsided, the level of Tregs will rise, and the level of DEL-1 molecules will also rise. So we want to know how they are related. The researchers then used a mouse model of periodontitis to study and found that the DEL-1 molecule can promote the regression of inflammation in the body, in other words, it can help the body return to a normal state. In this study, the researchers relied on this model to investigate the relationship between DEL-1 molecules and Tregs cells. Tregs cells, like DEL-1 molecules, increase their levels as inflammation subsides.
The researchers said that compared with mice carrying the DEL-1 molecule, the level of Tregs in mice lacking the molecule at birth will decrease, while the level of T cells related to inflammation—Th17 will increase. The level of Tregs in mice lacking this molecule can be restored by injection of DEL-1. This association may provide clues (not evidence) to the direct relationship between DEL-1 and Tregs, and there is a special reciprocity between Tregs and Th17 cells, so researchers do not know whether DEL-1 molecules will react to Tregs or Th17 cells.
In order to confirm this association, the researchers used cultured mouse cells to conduct experiments to observe whether DEL-1 molecules affect the development of T cells into mature Th17 cells or Tregs cells, because DEL-1 molecules do not seem to directly affect Th17. The production of cells and its effect on Tregs surprised researchers. When researchers studied human cells, they also found that the production of Tregs would continue to increase in the presence of DEL-1. In addition, the researchers found that the immunosuppressive function of T cells (which is supported by Tregs cells) is enhanced when DEL-1 is present.
The researchers believe that DEL-1 can support the activity of Tregs. Then they conducted a series of experiments to reveal more detailed information about the signaling pathways that DEL-1 plays. They found that DEL-1 can interact with a type of T cell surface. Special molecular interaction, the molecule can induce the transcription factor RUNX1 to promote the expression and stability of the main regulator FOXP3 of Tregs cells. Without FOXP3, there would be no Tregs in the body; therefore, DEL-1 molecules can exert epigenetic effects by removing methylated groups (small molecule tags) located in gene regions to stabilize FOXP3 molecules.
The loss of FOXP3 is indeed associated with serious human diseases, such as IPEX syndrome, which is an X-chromosome-related disease caused by FOXP3 mutations, which makes the level of Tregs in the patient's body become lower, and Patients also frequently develop a variety of autoimmune diseases. Although researchers initially studied mouse models of periodontal disease, they believed that the association between DEL-1 and Tregs might be more common, so they investigated this in a mouse model of acute lung inflammation. Researchers also found the same pattern, that is, the lack of DEL-1 is directly related to the severe reduction in the number of Tregs and the inability to effectively resolve inflammation.
Later researchers hope to study this mechanism more deeply to detect whether the source of DEL-1 will affect the regulation of Tregs. In addition, other researchers also want to apply these findings to the study of autoimmune disease models. Autoimmune diseases can be effectively controlled by shifting to the balance of immunosuppression. In the end, the researcher Hajishengallis believes that DEL-1 can not only be used in the study of periodontitis and inflammatory diseases, but also as a potential new target for the treatment of autoimmune diseases.