Chinese scholars have made new progress in the pathogenesis and treatment strategies of chronic sinusitis

Fig.
1 Novel pathogenesis of type 2 immune response driving disease progression in the nasal immune microenvironment of eCRSwNP

Fig.
2 ALOX15 inhibitors can treat type 2 inflammatory diseases in vivo and in vitro models

With the support of the National Natural Science Foundation of China (grant numbers: 82071027, 82101200, 82071791, 91542117, U20A20374), the team of Dr.
Wang Weiqing and Professor Lu Wei of the Department of Otolaryngology, Head and Neck Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and the team of Professor He Wei and Zhang Jianmin of the Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, have made new progress in the research field of pathogenesis and new therapeutic targets of chronic sinusitis.
Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis," published online
in the journal Nature Immunology 。 Links to papers: _istranslated="1">.

The research team established for the first time the nasal mucosal epithelial cells, mesenchymal cells and immune cells of three subtypes of chronic sinusitis: normal human, chronic sinusitis without nasal polyps, eosinophilic chronic sinusitis with nasal polyps and non-eosinophilic chronic sinusitis with nasal polyps, through single-cell transcriptome sequencing technology, and studied the internal molecular mechanisms affecting the development and subtype differentiation of chronic sinusitis.
Key factors within the local tissue microenvironment that affect disease progression in eosinophilic nasal polyps (eCRSwNP) are systematically defined (Figure 1).

Based on the results of single-cell sequencing analysis, the research team deeply explored the pathogenic mechanism and therapeutic new targets of diseases through a series of cytology, molecular biology and animal experiments
.
The results showed that ALOX15⁺ macrophages are the key nodes
that affect and regulate the occurrence and development of eCRSwNP diseases.
Through the mouse model of eosinophilic sinusitis, it was found that the application of ALOX15 inhibitors can effectively reduce the cytokine IL-4, IL-5, IL-13 and IgE levels in the blood, relieve type 2 inflammation, and have a good effect on eosinophilic sinusitis (Fig.
2).

The results of this study show that ALOX15 is expected to become a new drug target for the treatment of eCRSwNP
.