Cigarette smoke aggravates asthma by inducing memory-like type 3 innate lymphoid cells

Jongho Ham, Jihyun Kim, Kyoung Hee Sohn, In Won Park, Byoung Whui Choi, Doo Hyun Chung, Sang Heon Cho, Hye Ryun Kang, Jae Woo Jung, Hye Young Kim

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3852
JournalNature Communications
Issue number1
StatePublished - Dec 2022


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