Cigarette smoke extract contributes to the inception and aggravation of asthmatic inflammation by stimulating innate immunity

ABSTRACT

Purpose@#Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. @*Methods@#Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4 + T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. @*Results@#Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4 + T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3 + in CD4 + T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII + DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17 + ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. @*Conclusion@#In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.