title: Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.
abstract: The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of epidermal growth factor receptor and extracellular-signal regulated kinase, which were required for induction of IL-25, IL-33, and TSLP expression. In two AD models, Itln knockdown suppressed expression of Il-33, Tslp, and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of AD. We conclude that ITLN contributes to allergen-induced Il-25, Il-33, and Tslp expression in asthma and AD.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: L
authors.initials: L
authors.lastname: Yi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: D
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Huo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: H
authors.initials: H
authors.lastname: Di
authors.affiliation: Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Erle
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Key Laboratory of Respiratory Diseases, National Health and Family Planning Commission of the People's Republic of China, Wuhan, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhen
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae; D034741:RNA, Small Interfering / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D058851:GPI-Linked Proteins; C486701:IL25 protein, human; C432397:ITLN1 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D037102:Lectins; D034741:RNA, Small Interfering; D000094632:Thymic Stromal Lymphopoietin