title: Basophil-associated OX40 ligand participates in the initiation of Th2 responses during airway inflammation.
abstract: Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophils-primed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40(-/-) mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation.
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Di
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Lin
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China, and.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Department of Pediatrics, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China, xzw63@hotmail.com.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001491:Basophils / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053278:OX40 Ligand; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors
keywords: Basophils; OX40-OX40L; T helper cells; Th2 response; asthma; immunology; inflammation; lung
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