Science: In asthma, certain helper cells become disease triggers

Scientists identify the molecular cause of asthma
The symptoms of asthma are relatively easy to control, but a cure has not yet been achieved based on the available treatment approaches. The causes of the disease also remain unclear. However, in a recent study, researchers were able to identify the molecular mechanism that creates a type of immune cell that is involved in allergic diseases such as asthma.

The scientists around Professor Dr. Magdalena Huber from the Philipps University of Marburg was able to show in her studies that certain proteins that are involved in the development of immune cells lead to an imbalance in the supply of immune cells. Under the influence of the proteins, excessively special immune cells may be produced that are associated with the development of autoimmune diseases such as asthma. The researchers published their results in the journal "Nature Communications".

Control cell differentiation
By analyzing the molecular processes that lead to the differentiation of the so-called T helper cells, the scientists were able to gain some groundbreaking insights. T-helper cells normally contribute to the body's immune defense against, for example, worms and cancer, but they are also involved in autoimmune diseases and asthma, the experts explain. These immune cells arise from immature precursors and specialize in certain services when external stimuli stimulate them to mature, the scientists continue. This process is called cell differentiation.

Interaction of two proteins examined
According to the researchers, which cells develop during cell differentiation is controlled by the network-like interaction of genes that switch each other on and off. "In order to effectively combat allergic diseases, it is important to find out how the differentiation of the T helper cells is controlled genetically," said Prof. Huber. The research team has therefore examined the interaction of two proteins that have a significant influence on the differentiation of the T helper cells. They analyzed the effects of the so-called “interferon regulating factors” IRF1 and IRF4.

Opposing effects of the two proteins were examined
The scientists found that the two proteins work against each other when a certain type of T helper cell develops, the Th9 cell. These Th9 cells are characterized by the production of the protein interleukin 9 (IL-9) and the experiments have shown that IRF1 suppresses the production of IL-9, the researchers report. The IRF4 protein, on the other hand, promoted IL-9 production. This observation suggested that IRF1 and IRF4 compete for coupling to a gene that contains the building instructions for IL-9, reports the Philipps University of Marburg.

Effects on the development of asthma
In the mouse model, the researchers examined the consequences of the opposing activities of IRF1 and IRF4 for the development of asthma. Here they were able to demonstrate that IRF1 limits the pathogenic effect of Th9 cells. This suggests that "asthmatics have a disturbed balance between the two factors and therefore produce more asthma-promoting IL-9," explains the first author Lucia Campos Carrascosa from the Philipps University of Marburg.

New treatment options
"Our study proves that the molecular ratio between IRF1 and IRF4 influences the fate of Th9 cells," according to Prof. Die. This also opens up new possibilities for the treatment of allergic diseases such as asthma. In addition to the scientists from Marburg, the study also involved researchers from the University Clinic in Mainz, the Universities of Würzburg and Munich (LMU) and Japanese researchers from Osaka. (fp)

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