2. Academic Validation
  3. Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice

Stress granule assembly impairs macrophage efferocytosis to aggravate allergic rhinitis in mice

  • Nat Commun. 2025 Jul 1;16(1):5610. doi: 10.1038/s41467-025-60920-0.
Ye Zhou # 1,  Zixuan Yang # 2 3,  Yuanyuan Wang # 1,  Yue Dong # 1,  Tianyu Wang # 2,  Yunhui Li 1,  Caiquan Liang 2,  Yanfang Liu 1,  Zhixuan Li 1,  Shanrong Liu 1,  Liangchen Gui 1,  Yiwen Fan 1,  Ting Lei 1,  Kaiwei Jia 1,  Liyuan Zhang 1,  Mu Wang 1,  Wen Nie 1,  Long Chen 1,  Mingrui Ma 1,  Yanfeng Wu 1,  Cuiping Zhong 3,  Huanhai Liu 2,  Jin Hou 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Immunity and Inflammation, Second Military Medical University, Shanghai, 200433, China.
  • 2 Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Second Military Medical University, Shanghai, 200003, China.
  • 3 Department of Otolaryngology-Head and Neck Surgery, No. 940 Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou, 730000, China.
  • 4 National Key Laboratory of Immunity and Inflammation, Second Military Medical University, Shanghai, 200433, China. houjin@immunol.org.
  • # Contributed equally.
PMID: 40595582 DOI: 10.1038/s41467-025-60920-0
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.

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