한빛사논문
Jae Woo Shin, BS,1 Jihyun Kim, PhD,1 Seokjin Ham, PhD,2 Sun Mi Choi, MD, MS,3 Chang-Hoon Lee, MD, PhD,3 Jung Chan Lee, PhD,4 Ji Hyung Kim, PhD,5 Sang-Heon Cho, MD, PhD,6,7 Hye Ryun Kang, MD, PhD,6,7 You-Me Kim, PhD,8 Doo Hyun Chung, MD, PhD,9,10 Yeonseok Chung, PhD,11 Yoe-Sik Bae, PhD,12,13 Yong-Soo Bae, PhD,12,13 Tae-Young Roh, PhD,2,14 Taesoo Kim, PhD,15 Hye Young Kim, PhD,1,7*
1Laboratory of Mucosal Immunology in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
2Department of Life Sciences and Division of Integrative Biosciences & Biotechnology, Pohang University of Science & Technology (POSTECH), Pohang, Republic of Korea
3Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
4Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea
5College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
6Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
7Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
8Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
9Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
10Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
11Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
12Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, Republic of Korea
13Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
14SysGenLab Inc., Pohang, Republic of Korea
15Department of Life Science, Ewha Womans University, Seoul, Republic of Korea
*Corresponding author.
Abstract
Background
Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear.
Objective
This study aims to identify a key cellular player of air pollutant-induced asthma exacerbation and development.
Methods
We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite (HDM) and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry, RNA seq analysis. The roles of Sialic acid-binding, Ig-like lectin F (SiglecF)+ neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies.
Results
We show here that DEP exposure induces a unique population of lung granulocytes that co-express Ly-6G and sialic acid-binding, Ig-like lectin (Siglec)-F. These cells differ phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEP induces the local release of adenosine 5′-triphosphate (ATP), which is a damage-associated molecular pattern (DAMP) signal. ATP promotes the expression of SiglecF on neutrophils, and these SiglecF+ neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8 (which corresponds to murine SiglecF) expressing neutrophils and in the patients with asthma-COPD overlap (ACO).
Conclusion
SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting the populations could reverse or ameliorate asthma.
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