title: Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation.
abstract: The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Paediatrics, Shanghai Children's Medical Centre affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Di
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Paediatrics, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Paediatrics, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Xia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: T helper type 2 response; allergic airway inflammation; basophil; heme oxygenase-1