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Interactions between NCR+ILC3s and the Microbiome in the Airways Shape Asthma Severity

  • Jongho Ham (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Jihyun Kim (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Sungmi Choi (Interdisciplinary Program in Precision Public Health, Korea University) ;
  • Jaehyun Park (Interdisciplinary Program in Bioinformatics, Seoul National University College of Natural Sciences) ;
  • Min-gyung Baek (Interdisciplinary Program in Precision Public Health, Korea University) ;
  • Young-Chan Kim (Department of Internal Medicine, Seoul National University Hospital) ;
  • Kyoung-Hee Sohn (Department of Internal Medicine, Kyung Hee University Hospital) ;
  • Sang-Heon Cho (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Siyoung Yang (Department of Pharmacology, Ajou University School of Medicine) ;
  • Yong-Soo Bae (Center for Immune Research on Non-Lymphoid Organ (CIRNO), Sungkyunkwan University) ;
  • Doo Hyun Chung (Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul National University College of Medicine) ;
  • Sungho Won (Department of Public Health Sciences, Seoul National University) ;
  • Hana Yi (Interdisciplinary Program in Precision Public Health, Korea University) ;
  • Hye Ryun Kang (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Hye Young Kim (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2021.06.17
  • Accepted : 2021.07.16
  • Published : 2021.08.31
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Abstract

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)+ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR+ILC3 frequencies and microbial diversity in the lung. Sputum NCR+ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR+ILC3s may contribute to a healthy commensal diversity and normal lung function.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (2019R1A2C2087574 and SRC 2017R1A5A1014560).

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