Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice

Hiroo Wada, Masuo Nakamura, Shin Ichi Inoue, Akihiko Kudo, Tomoko Hanawa, Yoichiro Iwakura, Fumie Kobayashi, Hiroshi Kamma, Shigeru Kamiya, Kazuhiro Ito, Peter J. Barnes, Hajime Takizawa

Research output: Contribution to journalArticlepeer-review

Abstract

IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.

Original languageEnglish
Article number11508
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021

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