The cause of asthma and atopic dermatitis found! National Health Research Institutes of Taiwan study: Excessive expression of dephosphatase DUSP8
Asthma, allergic rhinitis and atopic dermatitis are known as the “Three Allergy Brothers” and are the most common allergic diseases affected by both genetic constitution and environmental factors. Statistics from the 2017 National Health Interview Survey (NHIS) of Taiwan Health Promotion Administration It was found that the asthma prevalence rate among asthmatic children under the age of 12 is as high as 5.6%, and an even greater proportion of them have been to the emergency room for asthma attacks within one year. .2%; among asthma patients over 12 years old, 22.6% had an asthma attack within one year. The respiratory tract of asthma patients is in a state of inflammation for a long time and is easily affected by irritants. If the asthma is not well controlled, asthma attacks may occur repeatedly. In severe cases, respiratory failure or even death may occur.
According to data released by the International Health Organization WHO, approximately 260 million people worldwide have suffered from asthma, resulting in approximately 450,000 deaths. In addition, about 5-20% of children worldwide suffer from atopic dermatitis, and the condition can continue into adults. Both diseases cause great distress to patients and consume a lot of medical resources. If the pathogenic mechanisms of the diseases can be found out, there will be opportunities to develop better medical methods and strategies.
A ten-year study by the team of Distinguished Researcher Tan Zehua and Associate Researcher Zhuang Huaijia of the National Health Research Institutes of Taiwan Immunology Research Center found that T lymphocytes with excessive expression of dephosphatase DUSP8 will prompt the cells to produce large amounts of the inflammatory cytokine IL-9. This can lead to asthma or atopic dermatitis. This research has been published in the world-renowned medical journal “Journal of Clinical Investigation (JCI)” in November this year (2023).
In order to study the role of DUSP8 in T cell-mediated immune responses, the research team spent many years creating T cell-specific DUSP8 gene knockout mice and used single-cell RNA sequencing, proteomics, and chromatin immunoprecipitation sequencing. Various biochemical experiments and analysis of mouse T cells found that DUSP8 directly dephosphorylates Pur-α, a transcriptional inhibitor of IL-9, causing Pur-α to leave the nucleus and be unable to perform its task of inhibiting IL-9 transcription, resulting in inflammatory cells. The hormone IL-9 is produced in large quantities.
Experiments have shown that DUSP8 is responsible for promoting the differentiation of helper Th9 cells and the allergic inflammatory response mediated by Th9 cells. The researchers collaborated with Dr. Qiu Xianyi from the Hsinchu Branch of National Taiwan University Hospital, Dr. Chen Minghan and Dr. Yu Wenguang from the Taipei Veterans General Hospital, and Dr. Chen Yiming from the Taichung Veterans General Hospital. They analyzed the T lymphocytes in the blood of patients with asthma and atopic dermatitis and found an overdose. The expressed dephosphatase DUSP8 regulates the transcriptional repressor Pur-α, causing a substantial increase in the inflammatory cytokine IL-9. These research results confirm that excessive dephosphatase DUSP8 is a key factor in the pathogenesis of asthma and atopic dermatitis.
The research team used T cell-specific DUSP8 gene knockout mice to conduct asthma experiments and found that when the dephosphatase DUSP8 was deleted in T lymphocytes, the inflammatory cytokine IL-9 in the mice decreased, and inflammation was significantly reduced. Therefore, if we can develop a method to inhibit the expression or activity of DUSP8 in T lymphocytes, it will have the potential to develop novel medical strategies to alleviate the symptoms of asthma or atopic dermatitis and promote the well-being of all people.
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