難治性喘息のマウスモデルにおけるgroup 2 innate lymphoid cells (ILC2)のフェノタイプ変化

抄録

It was reported that ILC2 were involved in induction of steroid-resistant allergic airway inflammation, one of endotypes of intractable asthma. We have reported that asthmatic responses including airway remodeling in 5 and 500 µg ovalbumin-induced models of BALB/c mice were sensitive and resistant, respectively, to dexamethasone, and that the steroid resistance was cancelled by anti-IL-5 mAb treatment. We also suggested that the major cellular source of IL-5 was ILC2 in the lung. In this study, it was analyzed whether function and molecular expression in ILC2 isolated from the steroid-resistant model were altered in comparison with those of the steroid-sensitive model. 1) In vitro IL-5-producing activity of ILC2 isolated from the lung of the steroid-resistant model in response to TSLP/IL-33 was considerably higher than those of the steroid-sensitive model. 2) FACS analyses revealed that expression of TSLP receptors (TSLPR) was up-regulated on the cell surface of ILC2 of the steroid-resistant model. 3) RNA-seq analyses revealed significant up-regulation of STAT5A mRNA expression in ILC2 of the steroid-resistant model. In conclusion, pro-inflammatory function of ILC2 was up-regulated in the intractable asthma. The up-regulation could be due to increases in TSLPR and STAT5A expression.