JCI: Scientists have discovered a new potential target for treating autoimmune diseases!

November 3, 2020 // -- The body's immune response is a balanced behavior, its excess will lead to inflammation or autoimmune diseases, too little will lead to the emergence of serious infections in the body, regulatory T cells, or Tregs cells are important to maintain this balance, it plays the role of "brake" in the body's immune response process to avoid excessive immune response.
Therefore, controlling the number and activity of Tregs is particularly important for maintaining the health of the body; in a recent study published in the international journal Journal of Clinical Investigation, scientists from institutions such as the University of Pennsylvania found that by targeting molecules called DEL-1 or as an effective way to help treat inflammation or suppress autoimmune responses, DEL-1 molecules promote Tregs and its immunosuppressive activity.
image source: Hajishengallis Laboratory researcher Hajishengallis said: 'In earlier studies we found an association where the level of Tregs rises and the level of the DEL-1 molecule rises as the inflammation subsides, so we want to know how the two are associated.'
The researchers then studied the periodontitis mouse model and found that the DEL-1 molecule promoted the withdrawal of inflammation in the body, in other words, it helped the body return to a normal state; in this study, the researchers relied on this model to explore the association between the DEL-1 molecule and the Tregs cells, which, like the DEL-1 molecule, increase their levels during inflammation subside.
researchers say that in mice that carry the DEL-1 molecule, the level of Tregs in mice born with the molecule missing decreases, while the level of inflammation-related T-cell-Th17 increases, and the level of Trgs in mice that are missing the molecule is restored by injecting DEL-1.
this association may provide clues (not evidence) about the direct association between DEL-1 and Tregs, and there is a special reciprocity between Trgs and Th17 cells, so researchers don't know if del-1 molecules react to Tregs or Th17 cells.
To confirm this association, the researchers used cultured mouse cells to study whether del-1 molecules affected the development of T cells into mature Th17 cells or Tregs cells, since del-1 molecules do not appear to directly affect the production of Th17 cells, and its effect on Trgs surprised researchers, when researchers studied human cells and found that in the presence of DEL-1 Tregs production will continue to increase.
also found that the immunosuppressive function of T-cells, which is supported by Tegs cells, was enhanced when DEL-1 was present.
researchers believe that DEL-1 can support Thergs' activity, and then they conducted a series of experiments to reveal more details about the signaling path path of DEL-1's role, and found that DEL-1 interacts with a specific molecule on the surface of T cells that induces the transcription factor RUNX. 1 Thus promoting the expression and stability of the main regulatory sub-FOXP3 of the Tregs cell, without FOXP3, the body would not have Tregs;
FOXP3 deficiency is indeed associated with serious diseases in humans, such as IPEX syndrome, an X chromosomal-associated disease caused by the FOXP3 mutation that causes lower levels of Tregs in the patient's body and frequent occurrence of a variety of autoimmune diseases.
Although the researchers were the first to study the periodontological mouse model, they believe that the association between DEL-1 and Tregs may be more common, so by investigating the association in mouse model organisms with acute lung inflammation, the researchers also found the same pattern, namely that the absence of DEL-1 was directly related to a severe reduction in Tregs' numbers and the inability of inflammation to be effectively addressed.
Later researchers wanted to study the mechanism more deeply to see if the source of DEL-1 could have an impact on regulating Tregs, and other researchers wanted to apply the findings to studies of models of autoimmune diseases, which can be effectively controlled by shifting to a balanced shift to immunosuppression.
'I don't think DEL-1 can be used not only in the study of periodontitis and inflammatory diseases, but also as a potential new target for the treatment of autoimmune diseases,' said Hajishengallis, a researcher at the University of York.
() Original source: Xiaofei Li et al, The DEL-1/beta 3 integrin axis promotes regulatory T cell responses when during resolution, Journal of Clinical Investigation (2020). DOI: 10.1172/JCI137530