Nasal congestion, runny nose, loss of smell? The cause of the endless "breathing pain" has been found!

Nasal congestion, runny nose, breathing only through the mouth, loss of smell, headaches and insomnia... Patients with chronic sinusitis and nasal polyps suffer from this series of symptoms and wonder "why does rhinitis always come back again and again." Little do they know that this type of allergic disease has long been a global problem.

On January 16, Professor Zhang Luo's team from the Department of Otolaryngology and Head and Neck Surgery at Beijing Tongren Hospital Affiliated to Capital Medical University, Professor Qi Hai's team from the School of Medicine of Tsinghua University, and Professor Wang Jianbin's team from the School of Life Sciences of Tsinghua University published their latest collaborative research results in Nature, "CD8+T cells expressing granzyme K promote recurrent airway inflammatory disease." They uncovered the "real culprit" behind this type of stubborn disease - a new type of memory CD8+T cells, and found a new immunological mechanism for the recurrent attacks of refractory chronic sinusitis and nasal polyps.

This "Chinese discovery" is expected to break the current situation of chronic sinusitis and nasal polyps, which are prone to recurrence, have many complications, and have poor quality of life for patients. By revealing new drug targets and new mechanisms of action, it provides an important theoretical basis and practical guide for changing the treatment pattern of chronic nasal diseases and even other allergic diseases.

On the morning of January 17, the "Beijing Tongren Hospital-Tsinghua University Nature Magazine Scientific Research Cooperation Results Release Conference" was held at Tsinghua University, and Professor Zhang Luo introduced the latest research results to Chinese and foreign media reporters.

Ten years of searching for the murderer

Chinese team reveals the truth behind stubborn nasal diseases

Chronic sinusitis is a common chronic nasal disease, whose symptoms usually include nasal congestion, purulent rhinorrhea, decreased or loss of smell, headache, etc. , affecting the quality of life of hundreds of millions of people worldwide.

Existing treatments, such as nasal sprays or oral hormone drugs, endoscopic nasal surgery, etc., can relieve symptoms to a certain extent, but they are of limited effect for about 30 million patients with refractory chronic sinusitis and nasal polyps, and are prone to relapse after treatment. These patients are often accompanied by complications such as asthma, which seriously affects their daily life and work.

For a long time, what exactly causes the prolonged recurrence of refractory chronic sinusitis and nasal polyps and how to find new treatment targets have been difficult problems that have plagued otolaryngologists around the world.

In order to overcome this problem and solve the "breathing pain" of tens of millions of patients, the clinical team of Beijing Tongren Hospital and the basic research team of Tsinghua University , after nearly a decade of unremitting exploration, finally discovered the key - an unusual memory CD8+T lymphocyte subset.

The "immune guard" in the body

But it is the "culprit" of disease recurrence

If white blood cells are compared to a "troop" that protects human health, then T lymphocytes are the "elite" that can carry out precise strikes. Among them, the so-called memory CD8+T lymphocytes are "special forces" that have become experienced in the fight against viruses and can quickly go into battle when the body encounters the same enemy again. They use perforins to punch holes in virus-infected cells and inject a "toxin" called granule protease B to kill these cells, thereby eliminating the virus. The human body also has an important defense system called complement, which is usually activated by antibodies that recognize viruses, kills cells by punching holes in the surface of virus-infected cells, and promotes inflammatory responses by recruiting white blood cells from the blood.

By analyzing the nasal polyp tissue of patients, the research team discovered a group of unusual memory CD8+T lymphocytes. These cells do not secrete the traditional granule proteinase B but secrete granule proteinase K , and appear in the polyp tissue every time the disease relapses. These T cells seem to recognize allergens and components of their own cells. More importantly, granule proteinase K can directly activate the body's complement system without antibodies, aggravating tissue cell damage and making the inflammatory response more and more intense. What's more tricky is that these cells that secrete granule proteinase K are particularly "active" and will continuously rush from the peripheral blood to the nasal tissue, repeating the cycle, turning a minor illness into a "difficult problem", causing sinusitis to recur and be difficult to cure.

Zhang Luo (second from right) and his colleagues during surgery. Photo courtesy of Beijing Tongren Hospital affiliated to Capital Medical University

Based on these important findings, the researchers further explored the possibility of treating the disease by inhibiting granule proteinase K. Animal experimental results showed that clearing or inhibiting granule proteinase K in CD8+T lymphocytes can significantly reduce inflammation and achieve good therapeutic effects. These results indicate that granule proteinase K and memory CD8+T cells that secrete this substance are important factors in the recurrence of refractory chronic sinusitis and nasal polyps, and are likely to become important biomarkers for predicting the progression of this type of disease and treatment response .

Groundbreaking research "aims for the future"

"China Discovery" is expected to change the treatment landscape

Based on this collaborative research between Beijing Tongren Hospital and Tsinghua University, Granulase K will be a new drug target for chronic sinusitis and nasal polyps and related allergic diseases. In the future, controlling inflammation and reducing recurrence by targeting Granulase K may become a new path to break through the treatment pattern of this type of disease.

This groundbreaking study, by discovering a new type of memory CD8+ T cell subset and analyzing the new pathway of granule proteinase K promoting inflammation by activating complement, proposed a new immunological mechanism behind chronic respiratory inflammation represented by chronic sinusitis and nasal polyps, laying a theoretical foundation for the development of new treatment methods. At the same time, the publication of this study marks that Chinese scholars are at the forefront of the world in the field of research and clinical transformation of refractory chronic sinusitis and nasal polyps.

Research Team

Professor Zhang Luo from Beijing Tongren Hospital , Professor Qi Hai from Tsinghua University, Associate Professor Wang Jianbin from Tsinghua University, and Associate Researcher Liu Xin from Tsinghua University are the co-corresponding authors of this article; Researcher Lan Feng from Beijing Tongren Hospital , and doctoral students Li Jizhou, Miao Wenxuan, and Sun Fei from the School of Life Sciences and the School of Basic Medicine of Tsinghua University are the co-first authors. Professor Wang Chengshuo, Professor Wang Xiangdong, and Chief Physician Duan Su from Beijing Tongren Hospital have made important contributions to the project.

This research was supported by the National Key R&D Program, Tsinghua University's Independent Research Program, the National Natural Science Foundation of China, the Shanxi Medical University-Tsinghua University School of Medicine Frontier Medical Biotechnology Research Project, the National Health Commission and the New Cornerstone Foundation.