Heme oxygenase‐1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2‐mediated allergic airway inflammation. Issue 3 (8th February 2016)

• Record Type: Journal Article
• Authors: Zhong, Wenwei; Di, Caixia; Lv, Jiajia; Zhang, Yanjie; Lin, Xiaoliang; Yuan, Yufan; Lv, Jie; Xia, Zhenwei
• Is Part Of: Immunology. Volume 147:Issue 3(2016)
• Page Start: 321
• Page End: 337
• Publication Date: 2016-02-08
• Subjects: allergic airway inflammation -- basophil -- heme oxygenase‐1 -- T helper type 2 response; Immunology -- Periodicals
• DOI: 10.1111/imm.12564
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: 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.