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  • 제21권4호
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  • Pages.26.1-26.28
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  • 2021
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell-Derived Cells Suppresses Rhinovirus-Induced Neutrophilic Airway Inflammation by Regulating Th1- and Th17-Type Responses

  • Ferdaus Mohd Altaf Hossain (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Seong Ok Park (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Hyo Jin Kim (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Jun Cheol Eo (Division of Biotechnology, College of Environmental & Biosource Science, Jeonbuk National University) ;
  • Jin Young Choi (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Maryum Tanveer (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Erdenebelig Uyangaa (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University) ;
  • Koanhoi Kim (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Seong Kug Eo (College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University)
  • 투고 : 2021.06.25
  • 심사 : 2021.08.05
  • 발행 : 2021.08.31
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초록

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4+ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

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과제정보

This study was supported by the Basic Science Research Program through National Research Foundation of Korea (NRF) grants funded by the Ministry of Education and the Ministry of Science and ICT (MSIT), Republic of Korea (2021R1A2B5B02001578, 2019R1A6A1A03033084, http://www.nrf.re.kr for Seong Kug Eo and 2020R1A6A3A13069626, http://www.nrf.re.kr for Seong Ok Park). The funder had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript. We thank Dr. Yoon-Young Choi, Center for University Research Facility (CURF) at Chonbuk National University for providing technical assistance for the FACS analysis.

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