The human immune system includes functionally specialized cellular defense mechanisms that protect the body against disease. These include the dendritic cells. Their main function is to present antigens to other immune cells, especially T cells, thereby activating a primary immune response. Dendritic cells are divided into type 1 (DC1) and type 2 (DC2) dendritic cells. Each type performs different functions: DC1 provides an immune response to bacteria and viruses, DC2 protects against fungal or parasitic infections. In a recent study conducted at the Cancer Research Institute of MedUni Vienna, researchers found that a particular group of proteins play a major role in the development of type 1 dendritic cells. This could open up new treatment options. in defense against viruses or bacteria but also for immunity against cancer.
Dendritic cells are formed from multipotent progenitor cells in the bone marrow. However, until now it has been difficult to know which proteins are responsible for this transition from stem cells to differentiated cells. The study, which has now been published in Cell death and differentiation, used animal models and molecular biology techniques such as RNA sequencing to show that a combination of two proteins called “c-Jun” and “JunB” are essential factors in the development of dendritic cells. 1. “The two proteins are transcription factors, DNA-binding molecules belonging to the Activator-Protein-1 (AP-1) family,” explains study author Philipp Novoszel, also associated with Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna. General hospital.
In order to analyze the role of these proteins, the c-Jun- and / or JunB gene was deleted in dendritic cells. “This showed that c-Jun and JunB are together, but not individually, essential for the development of DC1,” says second author of the study, Barbara Drobits of the Cancer Research Institute and CCC. The mechanism in detail: Working in a synergy never before described, the c-Jun / JunB transcription factor pair together control the development of DC1. “An expression analysis of DC1 devoid of c-Jun / JunB, showed changes in cell identity and a shift towards DC2.” At the same time, the immunological functions of DC1 were considerably reduced when c-Jun / JunB was lacking. Differences were also found in an infection model. In the animal model, deactivation of c-Jun / JunB protected against infection with Listeria monocytogenes.
“The results describe a previously unknown function of c-Jun / JunB in the development of dendritic cells. It has already been shown in previous studies that another member of the AP-1 family known as Batf3 is necessary for the development of DC1, in that it regulates the expression of the transcription factor IRF8. However, it was not clear which AP-1 protein Batf3 interacts with to perform this function. Our data now provide this “link. missing ”, in the sense that they indicate c-Jun / JunB as being Batf3’s tango partner”, summarize the authors of the study.
DC1s are essential for defense against bacteria and viruses as well as for immunity against cancer – a better understanding of the underlying biology could therefore provide promising new therapeutic approaches for future clinical applications.
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