2. Academic Validation
  3. Eosinophil extracellular traps drive asthma progression through neuro-immune signals

Eosinophil extracellular traps drive asthma progression through neuro-immune signals

  • Nat Cell Biol. 2021 Oct;23(10):1060-1072. doi: 10.1038/s41556-021-00762-2.
Yiwen Lu  # 1 2,  Yijiao Huang  # 1 3,  Jiang Li  # 1 2,  Jingying Huang  # 1 2,  Lizhi Zhang  # 1 3,  Jingwei Feng 1 2,  Jiaqian Li 1 2,  Qidong Xia 1 2,  Qiyi Zhao 4 5 6,  Linjie Huang 1 3 7,  Shanping Jiang 8 9 10,  Shicheng Su 11 12 13 14
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 2 Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 3 Department of Pulmonary and Critical Care Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4 Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 6 Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
  • 7 Institute of Pulmonary Diseases, Sun Yat-Sen University, Guangzhou, China.
  • 8 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. jiangshp@mail.sysu.edu.cn.
  • 9 Department of Pulmonary and Critical Care Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. jiangshp@mail.sysu.edu.cn.
  • 10 Institute of Pulmonary Diseases, Sun Yat-Sen University, Guangzhou, China. jiangshp@mail.sysu.edu.cn.
  • 11 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. sushch@mail.sysu.edu.cn.
  • 12 Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. sushch@mail.sysu.edu.cn.
  • 13 Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. sushch@mail.sysu.edu.cn.
  • 14 Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China. sushch@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 34616019 DOI: 10.1038/s41556-021-00762-2
Abstract

Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25-ILK-PKCα-CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.

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