Abstract

Although cigarette smoking is known to exacerbate asthma, only a few clinical asthma studies have been conducted involving smokers. Here we show, by comparing paired sputum and blood samples from smoking and non-smoking patients with asthma, that smoking associates with significantly higher frequencies of pro-inflammatory, natural-cytotoxicity-receptor-non-expressing type 3 innate lymphoid cells (ILC3) in the sputum and memory-like, CD45RO-expressing ILC3s in the blood. These ILC3 frequencies positively correlate with circulating neutrophil counts and M1 alveolar macrophage frequencies, which are known to increase in uncontrolled severe asthma, yet do not correlate with circulating eosinophil frequencies that characterize allergic asthma. In vitro exposure of ILCs to cigarette smoke extract induces expression of the memory marker CD45RO in ILC3s. Cigarette smoke extract also impairs the barrier function of airway epithelial cells and increases their production of IL-1β, which is a known activating factor for ILC3s. Thus, our study suggests that cigarette smoking increases local and circulating frequencies of activated ILC3 cells, plays a role in their activation, thereby aggravating non-allergic inflammation and the severity of asthma.

Cigarette smoking may exacerbate asthma, but the underlying mechanisms have not been studied extensively in human patients. Here authors show that type 3 innate lymphoid cells with activated phenotypes are found in the sputum and blood of smokers in higher frequencies, which might result in the aggravation of asthma.

Details

Title
Cigarette smoke aggravates asthma by inducing memory-like type 3 innate lymphoid cells
Author
Ham, Jongho 1   VIAFID ORCID Logo  ; Kim, Jihyun 2   VIAFID ORCID Logo  ; Sohn, Kyoung-Hee 3   VIAFID ORCID Logo  ; Park, In-Won 4   VIAFID ORCID Logo  ; Choi, Byoung-Whui 5 ; Chung, Doo Hyun 6 ; Cho, Sang-Heon 7 ; Kang, Hye Ryun 7   VIAFID ORCID Logo  ; Jung, Jae-Woo 4   VIAFID ORCID Logo  ; Kim, Hye Young 8   VIAFID ORCID Logo 

 Seoul National University College of Medicine, Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
 Seoul National University College of Medicine, Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
 Kyung Hee University Medical Center, Department of Internal Medicine, Seoul, Republic of Korea (GRID:grid.411231.4) (ISNI:0000 0001 0357 1464) 
 Chung-Ang University College of Medicine, Department of Internal Medicine, Seoul, South Korea (GRID:grid.254224.7) (ISNI:0000 0001 0789 9563) 
 Chung-Ang University College of Medicine, Department of Internal Medicine, Seoul, South Korea (GRID:grid.254224.7) (ISNI:0000 0001 0789 9563); Chung-Ang University H.C.S. Hyundae l Hospital, Department of Internal Medicine, Namyangju, South Korea (GRID:grid.254224.7) (ISNI:0000 0001 0789 9563) 
 Seoul National University College of Medicine, Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Pathology, Seoul, South Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul, South Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
 Seoul National University Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X); Seoul National University Hospital, Department of Internal Medicine, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
 Seoul National University College of Medicine, Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2684300510
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.