Studies on regulation of neutrophilic airway inflammation in severe asthma and chronic obstructive pulmonary disease (COPD)

用小鼠模型分析重症哮喘和慢性阻塞性肺疾病(COPD)的特征--中性粒细胞炎症，并评价其调节作用。令人意想不到的是，即使长期将香烟烟雾与感染因子联合给予小鼠，也无法建立良好的COPD模型。另一方面，在严重哮喘的小鼠模型中，中性粒细胞参与了暴露于变应原数小时后引起的呼吸道阻塞。还发现巨噬细胞衍生的趋化因子参与了中性粒细胞的气道炎症。此外，中性粒细胞炎症被内源性产生的抗炎分子白介素10抑制。接下来，开始了一种治疗哮喘的新的细胞免疫疗法的开发：体外诱导脾细胞产生IL-10的T淋巴细胞的方法。

Neutrophilic airway inflammation, a characteristic feature of severe asthma and chronic obstructive pulmonary disease (COPD), was analyzed using murine models, and regulation of the neutrophilic inflammation was evaluated. Unexpectedly, a good COPD model could not be developed even when cigarette smoke was co-administered with an infection factor to mice for a long term. On the other hand, in a murine model of severe asthma, neutrophils were involved in airway obstruction induced several hours after exposure to allergen. It was also found that macrophage-derived chemokines were involved in the neutrophilic airway inflammation. In addition, the neutrophilic inflammation was suppressed by an anti-inflammatory molecule, interleukin (IL)-10, which was endogenously produced. Next, development of a new cellular immunotherapy for asthma was started: Method for induction of IL-10-producing T lymphocytes from spleen cells was developed in vitro.