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JAK3 inhibitor suppresses multipotent ILC2s and attenuates steroid-resistant asthma
- Title
- JAK3 inhibitor suppresses multipotent ILC2s and attenuates steroid-resistant asthma
- Authors
- Kim; Jihyun; Ham; Jongho; Kang; Hye Ryun; Bae; Yong-Soo; TaeSoo; Hye Young
- Ewha Authors
- 김태수
- SCOPUS Author ID
- 김태수
- Issue Date
- 2023
- Journal Title
- Science Advances
- ISSN
- 2375-2548
- Citation
- Science Advances vol. 9, no. 51
- Publisher
- American Association for the Advancement of Science
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Steroids are the standard treatment for allergic airway inflammation in asthma, but steroid-refractory asthma poses a challenge. Group 2 innate lymphoid cells (ILC2s), such as T helper 2 (TH2) cells, produce key asthma-related type 2 cytokines. Recent insights from mouse and human studies indicate a potential connection between ILC2s and steroid-resistant asthma. Here, we highlight that lung ILC2s, rather than TH2 cells, can develop steroid resistance, allowing them to persist and maintain their disease-driving activity even during steroid treatment. The emergence of multipotent IL-5+IL-13+IL-17A+ ILC2s is associated with steroid-resistant ILC2s. The Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT) 3, 5, and 6 pathways contribute to the acquisition of steroid-resistant ILC2s. The JAK3 inhibitor reduces ILC2 survival, proliferation, and cytokine production in vitro and ameliorates ILC2-driven Alternaria-induced asthma. Furthermore, combining a JAK3 inhibitor with steroids results in the inhibition of steroid-resistant asthma. These findings suggest a potential therapeutic approach for addressing this challenging condition in chronic asthma. Copyright © 2023 The Authors.
- DOI
- 10.1126/sciadv.adi3770
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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