Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice
Abstract Cytoplasmic stress granules (SG) assemble in response to stress-induced translational arrest and are key signaling hubs orchestrating cell fate and regulating various physiological and pathological processes. However, the role of SG formation in the progression of allergic diseases is incom...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60920-0 |
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| author | Ye Zhou Zixuan Yang Yuanyuan Wang Yue Dong Tianyu Wang Yunhui Li Caiquan Liang Yanfang Liu Zhixuan Li Shanrong Liu Liangchen Gui Yiwen Fan Ting Lei Kaiwei Jia Liyuan Zhang Mu Wang Wen Nie Long Chen Mingrui Ma Yanfeng Wu Cuiping Zhong Huanhai Liu Jin Hou |
| author_facet | Ye Zhou Zixuan Yang Yuanyuan Wang Yue Dong Tianyu Wang Yunhui Li Caiquan Liang Yanfang Liu Zhixuan Li Shanrong Liu Liangchen Gui Yiwen Fan Ting Lei Kaiwei Jia Liyuan Zhang Mu Wang Wen Nie Long Chen Mingrui Ma Yanfeng Wu Cuiping Zhong Huanhai Liu Jin Hou |
| author_sort | Ye Zhou |
| collection | DOAJ |
| description | Abstract Cytoplasmic stress granules (SG) assemble in response to stress-induced translational arrest and are key signaling hubs orchestrating cell fate and regulating various physiological and pathological processes. However, the role of SG formation in the progression of allergic diseases is incompletely understood. Here, by analyzing the nasal tissues of allergic rhinitis (AR) mouse models and AR patients, we find that SGs assemble specifically in the macrophages within the nasal mucosa and promote AR progression by restraining the efferocytotic ability of macrophages, ultimately resulting in reduced Mres generation and IL-10 production. Mechanistically, intracellular m7G-modified Lrp1 mRNA, encoding for a typical efferocytosis receptor, is transported by the m7G reader QKI7 into stress-induced SGs, where Lrp1 mRNA is sequestered away from the translation machinery, ultimately resulting in reduced macrophage efferocytosis. Therefore, SG assembly impairs macrophage efferocytosis and aggravates AR, and the inhibition of SGs bears considerable potential in the targeted therapy. |
| format | Article |
| id | doaj-art-0c88d94d4d70466e985dc2045b34fc14 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-0c88d94d4d70466e985dc2045b34fc142025-08-20T03:03:44ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-60920-0Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in miceYe Zhou0Zixuan Yang1Yuanyuan Wang2Yue Dong3Tianyu Wang4Yunhui Li5Caiquan Liang6Yanfang Liu7Zhixuan Li8Shanrong Liu9Liangchen Gui10Yiwen Fan11Ting Lei12Kaiwei Jia13Liyuan Zhang14Mu Wang15Wen Nie16Long Chen17Mingrui Ma18Yanfeng Wu19Cuiping Zhong20Huanhai Liu21Jin Hou22National Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, No. 940 Hospital of Joint Logistics Support Force of People’s Liberation ArmyDepartment of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Second Military Medical UniversityNational Key Laboratory of Immunity and Inflammation, Second Military Medical UniversityAbstract Cytoplasmic stress granules (SG) assemble in response to stress-induced translational arrest and are key signaling hubs orchestrating cell fate and regulating various physiological and pathological processes. However, the role of SG formation in the progression of allergic diseases is incompletely understood. Here, by analyzing the nasal tissues of allergic rhinitis (AR) mouse models and AR patients, we find that SGs assemble specifically in the macrophages within the nasal mucosa and promote AR progression by restraining the efferocytotic ability of macrophages, ultimately resulting in reduced Mres generation and IL-10 production. Mechanistically, intracellular m7G-modified Lrp1 mRNA, encoding for a typical efferocytosis receptor, is transported by the m7G reader QKI7 into stress-induced SGs, where Lrp1 mRNA is sequestered away from the translation machinery, ultimately resulting in reduced macrophage efferocytosis. Therefore, SG assembly impairs macrophage efferocytosis and aggravates AR, and the inhibition of SGs bears considerable potential in the targeted therapy.https://doi.org/10.1038/s41467-025-60920-0 |
| spellingShingle | Ye Zhou Zixuan Yang Yuanyuan Wang Yue Dong Tianyu Wang Yunhui Li Caiquan Liang Yanfang Liu Zhixuan Li Shanrong Liu Liangchen Gui Yiwen Fan Ting Lei Kaiwei Jia Liyuan Zhang Mu Wang Wen Nie Long Chen Mingrui Ma Yanfeng Wu Cuiping Zhong Huanhai Liu Jin Hou Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice Nature Communications |
| title | Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| title_full | Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| title_fullStr | Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| title_full_unstemmed | Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| title_short | Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| title_sort | stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice |
| url | https://doi.org/10.1038/s41467-025-60920-0 |
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