National Health Research Institutes (NHRI) researchers yesterday said they have identified a key mechanism that controls the production of a particular cytokine — small proteins utilized in cell signal tranmission — which could be used to develop therapeutic strategies to treat autoimmune diseases.
Interleukin 17A (IL-17A) cytokine is a proinflammatory cytokine produced by activated T cells, a subset of white blood cells that are part of the body’s immune system.
The team identified an upstream target, the “AhR-RORγt complex,” that controls the overproduction of IL-17A inside the cells.
Photo: Lin Huei-chin, Taipei Times
They said small molecules that can inhibit the AhR-RORγt complex could be cost-effective therapeutic agents for IL-17A-mediated autoimmune diseases.
Autoimmune diseases — where the immune system mistakenly attacks healthy cells or organs — rank third in the list of top 10 catastrophic illnesses in Taiwan, NHRI distinguished research fellow Tan Tse-hua (譚澤華) said.
There are about 400,000 to 500,000 patients with autoimmune diseases such as lupus, rheumatoid arthritis and psoriatic arthritis, who require treatment all their lives, he said.
After seven years of work, Tan and assistant investigator Chuang Huai-chia (莊懷佳) identified the key mechanism controlling the overproduction of IL-17A.
In 2011, their team discovered that the kinase MAP4K3/GLK is a key pathogenic factor for autoimmune diseases, and GLK overexpression in T cells induces a novel-signaling cascade for inflammation and autoimmune responses.
Pathogenic cytokine IL-17A levels increased in the serum of GLK transgenic mice, and knockout-mouse experiments showed that overexpression of the kinase GLK induces the AhR-RORγt complex and subsequent IL-17A overproduction, leading to autoimmune diseases, Chuang said.
Most importantly, the AhR-RORγt complex causes overproduction of IL-17A, but not of other cytokines, Tan said.
That shows that the AhR-RORγt complex is a novel target for autoimmune disease therapies, he said.
The team applied for a patent on their discovery and its clinical applications with the US Patent and Trademark Office.
They said they would continue to develop inhibitors of the AhR-RORγt complex and plan to collaborate with biotech companies in the hopes of developing a new treatment for autoimmune diseases.
A research paper outlining the discovery, written by Chuang, Tsai Ching-yi, Hsueh Chia-hsin and Tan was published in Science Advances on Sept. 12.
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