NHRI researchers find DUSP8 is a key to the induction of asthma and atopic dermatitis

  • Date: 2023-11-21
  • Update: 2023-11-21
  • Source: 國家衛生研究院
  • Views: 332

NHRI researchers find DUSP8 is a key to the induction of asthma and atopic dermatitis

November 23, 2023

Scientists with Taiwan's National Health Research Institutes (NHRI) have discovered DUSP8 is a key to the pathogenesis of asthma and atopic dermatitis.

Asthma affected at least 262 million people and caused 455,000 deaths around the world in 2019, according to the World Health Organization. In addition, atopic dermatitis affects about 20% of children and up to 10% of adults in the world. Both diseases are incurable and incur high medical costs. Understanding the disease pathogeneses will help development of novel therapies for asthma and atopic dermatitis.

After ten years of indefatigable research, distinguished investigator Dr. Tse-Hua Tan and associate investigator Dr. Huai-Chia Chuang, both with NHRI’s Immunology Research Center, recently discovered that a key phosphatase, DUSP8, controls the induction of asthma and atopic dermatitis. They found that DUSP8 overexpression in T cells induces production of the proinflammatory cytokine IL-9, leading to asthma or atopic dermatitis. Their work was published in the November issue of the Journal of Clinical Investigation.

To study the role of DUSP8 in T-cell-mediated immune responses, Dr. Tan’s research team worked since 2013 to generate T-cell-specific DUSP8 conditional knockout (DUSP8 cKO) mice. The research team characterized T cells of DUSP8 cKO mice by single-cell RNA sequencing (scRNA-seq), mass spectrometry-based analysis, chromatin-immunoprecipitation sequencing (ChIP-seq), and multiple biochemical experiments. They found that DUSP8 interacts with and dephosphorylates the transcriptional repressor Pur-α, resulting in the nuclear export of Pur-α and subsequent IL-9 transcriptional activation. They demonstrated that DUSP8 controls T helper 9 cell differentiation and Th9-mediated allergic responses. And they validated that DUSP8 overexpression and DUSP8-Pur-α interaction indeed occur in the peripheral blood T cells of patients with asthma or atopic dermatitis, contributing to IL-9 overproduction in patients’ T cells. These findings indicate that DUSP8 overexpression plays a critical role in the pathogenesis of asthma and atopic dermatitis.

The research team also created an allergic asthma model using DUSP8 cKO mice. They found that IL-9 production and Th9-mediated inflammation are reduced by DUSP8 conditional knockout. These results suggest that an inhibitor that suppresses DUSP8 expression or activity in T cells may be a potential therapeutic drug for asthma and atopic dermatitis. This novel therapeutic approach could lead to precision medicine of asthma and atopic dermatitis.

In this work, the research team collaborated with others at NHRI and with Drs. Hsien-Yi Chiu, Ming-Han Chen, Wen-Kuang Yu, and Yi-Ming Chen: four physician scientists from National Taiwan University Hospital’s Xinzhu Branch, Taipei Veterans General Hospital, and Taichung Veterans General Hospital.