한빛사논문
- 조회373
Hyung-Geun Moon,1* Seung-jae Kim,1 Ki-Hyun Kim,1 Young-Mee Kim,2 Jalees Rehman,2 Hyun Lee,3 Yi-ChienWu,4 Steve Seung-Young Lee,4 John W. Christman,5 Steven J. Ackerman,6 Minhyung Kim,7 Sungyoung You,7 and Gye Young Park1,8 *
1Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
2Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL, USA
3Center for Biomolecular Sciences, and Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
4College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
5Section of Pulmonary, Critical Care, and Sleep Medicine, the Ohio State University, Davis Heart and Lung Research Center, Columbus, OH, USA
6Department of Biochemistry and Molecular Genetics, and Medicine, University of Illinois at Chicago, Chicago, IL, USA
7Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
8Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA
*Correspondence: Hyung-Geun Moon, Gye Young Park
Abstract
Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated.
Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation.
Methods: For the study, we utilized the IRB-approved protocol for human subsegmental bronchoprovocation with allergen (SBP-AG), mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, sc-RNA-sequencing, biophysical, and immunological analyses.
Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared to classical AM, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cells derived-CCL26 via a receptor-ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia.
Conclusion: These findings indicate that the CCL26-CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-04-20)
- 국외 연구진
- 의약학 > 응용의학
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