한빛사논문
Jihyun Kim 1 2, Jongho Ham 1 2 3, Hye Ryun Kang 2 4, Yong-Soo Bae 3 5, TaeSoo Kim 6, Hye Young Kim 1 2 3 *
1Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
2Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea.
3Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, South Korea.
4Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
5Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.
6Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul, South Korea.
*Corresponding author: correspondence to Hye Young Kim
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.
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