氯暴露通过固有淋巴细胞和cd11c介导的巨噬细胞加重哮喘炎症
2019/09/09
背景：氯在日常生活中被广泛用作消毒剂。然而，长期接触氯产品会加重过敏th2炎症和气道高反应性(AHR)。呼吸道先天淋巴细胞(ILCs)与病毒感染、污染和营养过剩有关，是哮喘发病的原因之一，但长期氯暴露是否能激活先天免疫细胞尚不清楚。本研究的目的是利用小鼠卵清蛋白(OVA)敏化/挑战模型，评估氯吸入对ILCs、巨噬细胞等先天免疫功能的影响与哮喘发生的关系。
方法：六周大的雌性BALB/c小鼠经吸入存在或不存在慢性低剂量氯（5%次氯酸钠溶液）的卵清蛋白OVA自然汽化气体致敏。评估小鼠AHR、BALF气道炎症细胞、肺内ILCs和巨噬细胞的数量。
结果：与经卵清蛋白（OVA）处理的小鼠(OVA组)相比，经卵清蛋白处理的小鼠且暴露于氯(Cl+OVA组)后，AHR和嗜酸性炎症增强。与OVA组相比，Cl+OVA组2型辅助T细胞、ILC2s和ILC3s的数量增加。与OVA组相比，Cl+OVA组CD11cint巨噬细胞明显增多。氯膦酸盐对巨噬细胞的清除导致ILC2s和ILC3s的减少，通过过继转移CD11cint巨噬细胞恢复ILC2s和ILC3s的数量。
结论：慢性氯吸入可通过动员促炎巨噬细胞进入肺，刺激第2组和第3组ILCs，加重哮喘性气道炎症。
(Allergy. 2019 Aug 11. doi: 10.1111/all.14017)
Aggravation of asthmatic inflammation by chlorine exposure via innate lymphoid cells and CD11cintermediate macrophages.
Shim JS, Lee HS, Park DE, Lee JW, Bae B, Chang Y, Kim J, Kim HY, Kang HR.
Abstract
BACKGROUND:Chlorine is widely used in daily life as disinfectant. However, chronic exposure to chlorine products aggravates allergic TH 2 inflammation and airway hyperresponsiveness (AHR). Innate lymphoid cells (ILCs) in airways contribute to the inception of asthma in association with virus infection, pollution, and excess of nutrient but it is not known whether chronic chlorine exposure can activate innate immune cells. The aim of this study is to evaluate the impact of chlorine inhalation on the innate immunity such as ILCs and macrophages in relation with the development of asthma by using murine ovalbumin (OVA) sensitization/challenge model.
METHODS:Six-week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure by inhalation of naturally vaporized gas of 5% sodium hypochlorite solution. AHR, airway inflammatory cells from BALF and the population of ILCs and macrophages in the lung were evaluated.
RESULTS:The mice exposed to chlorine with OVA (Cl+OVA group) showed enhanced AHR and eosinophilic inflammation compared to OVA-treated mice (OVA group). The population of TH 2 cells, ILC2s and ILC3s increased in Cl+OVA group compared to OVA group. CD11cint macrophages also remarkably increased in Cl+OVA group compared to OVA group. The deletion of macrophages by clodronate resulted in reduction of ILC2s and ILC3s population which was restored by adoptive transfer of CD11cint macrophages.
CONCLUSIONS:Chronic chlorine inhalation contributes to the exacerbation of airway inflammation in asthmatic airway by mobilizing pro-inflammatory macrophage into the lung as well as stimulating group 2 and 3 ILCs.
