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Adv. Sci., Jan 26 2024, | https://doi.org/10.1002/advs.202308978
Innate Immune Training Initiates Efferocytosis to Protect against Lung Injury
Yoon-Young Kang 1,2, Dong-Young Kim 1, Sang-Yong Lee 1,2, Hee-Joong Kim 1,2, Taehawn Kim 1, Jeong A Cho 1, Taewon Lee 3, Eun Young Choi 1,2
1Department of Biomedical Sciences, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505, Republic of Korea.
2Department of Microbiology, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505, Republic of Korea.
3Division of Applied Mathematical Sciences, College of Science and Technology, Korea University, Sejong, 30019, Republic of Korea.
CORRESPONDING AUTHOR : Eun Young Choi
Abstract
Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with β-glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin-induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. β-Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with β-glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of β-glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury-mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury-mediated disorders.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-01-30)
- 국내 연구진
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