Li Yan, Wang Zaichuan, Duan Su, Wang Xue, Zhang Yuling, Bachert Claus, Zhang Nan, Wang Wei, Ying Sun, Lan Feng, Wang Chengshuo, Zhang Luo
Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China.
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Nat Commun. 2025 Aug 2;16(1):7108. doi: 10.1038/s41467-025-62532-0.
Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that toll-like receptor 4 (TLR4)ILC2s, with similar markers to their human counterparts, expresse memory cell markers, persist over time, and respond more vigorously to a secondary unrelated antigen challenge in the mouse model. Genetic ablation of TLR4 or blockade by anti-TLR4 antibodies leads to the reduction of IL-13 expression from ILC2s and mucus production in mice. The assay for transposase-accessible chromatin sequencing further confirms the importance of accessible TLR4 gene loci and its down-stream signaling pathway in maintaining trained immunity of TLR4ILC2s after repeated stimulation by HDM. Taken together, TLR4 has a function in trained immunity maintenance within ILC2s, which may contribute to disease chronicity through a non-specific immunological memory.
第2组固有淋巴细胞（ILC2s）直接参与2型炎症性气道疾病的局部炎症反应。在此，我们通过单细胞RNA测序在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）以及记忆性炎症小鼠模型中鉴定出ILC2亚群。我们发现，与人类对应细胞具有相似标志物的Toll样受体4（TLR4）⁺ ILC2s表达记忆细胞标志物，随时间持续存在，并且在小鼠模型中对二次无关抗原刺激反应更为强烈。TLR4的基因敲除或抗TLR4抗体阻断导致小鼠ILC2s中IL-13表达及黏液分泌减少。转座酶可及染色质测序分析进一步证实了可及的TLR4基因位点及其下游信号通路在维持经屋尘螨反复刺激后的TLR4⁺ ILC2s的训练免疫中的重要性。综上所述，TLR4在ILC2s的训练免疫维持中发挥作用，这可能通过非特异性免疫记忆导致疾病慢性化。
