title: Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.
abstract: Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway.
authors.affiliation: Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; Asan Institute for Life Science, Seoul 05505, Korea;
authors.forename: Gyong Hwa
authors.initials: GH
authors.lastname: Hong
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; and.
authors.forename: Hyouk-Soo
authors.initials: HS
authors.lastname: Kwon
authors.affiliation: Asan Institute for Life Science, Seoul 05505, Korea;
authors.forename: Keun-Ai
authors.initials: KA
authors.lastname: Moon
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; and.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Asan Institute for Life Science, Seoul 05505, Korea;
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Asan Institute for Life Science, Seoul 05505, Korea;
authors.forename: Kyoung Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; Asan Institute for Life Science, Seoul 05505, Korea;
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ha
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; and.
authors.forename: Tae-Bum
authors.initials: TB
authors.lastname: Kim
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; and.
authors.forename: Hee-Bom
authors.initials: HB
authors.lastname: Moon
authors.affiliation: Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Heung Kyu
authors.identifier: http://orcid.org/0000-0002-3977-1510
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; and yscho@amc.seoul.kr.
authors.forename: You Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D054418:Chemokine CCL20 / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D051152:Clusterin / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology
chemical_list: D054418:Chemokine CCL20; D051152:Clusterin