Development of asthma is mainly dominated by the type 2 immune response governed by Th2 cells and group 2 innate lymphoid cells (ILC2), both of which produce interleukin (IL)-4, IL-5 and IL-13. Although the type 2 immune response is generally well controlled by glucocorticoids, it has been suggested that 5-10% of asthma patients receiving medical care are resistant or insensitive to the steroids. A certain patient population with severe asthma exhibits persistent existence of ILC2 in the lung despite glucocorticoid therapy. The pathogenic changes in ILC2 exhibiting steroid resistance should be associated with the severity. However, mechanisms of pathogenic changes in ILC2 have not been fully elucidated. We have established a murine model of severe asthma, which shows airway remodeling and ILC2 proliferation in the lung, and those parameters were insensitive to dexamethasone treatment. The lung ILC2 displayed marked up-regulation of JAK3 and STAT5. Moreover, mRNA level of Bcl-2, an anti-apoptotic molecule that is a downstream molecule of STAT5, was also significantly upregulated. The JAK3-STAT5-Bcl-2 pathway should suppress the induction of apoptosis by glucocorticoids, leading to the persistent survival of ILC2 in the lung. Therefore, the JAK3-STAT5-Bcl-2 pathway could be a therapeutic target for steroid-resistant severe asthma.