title: IL-25 regulates the polarization of macrophages and attenuates obliterative bronchiolitis in murine trachea transplantation models.
abstract: Obliterative bronchiolitis (OB) remains the major limitations for the long-term survival of allografts after lung transplantation. Th17 cells and IL-17 have been recognized as mediators of the development of OB in both animal models and human beings. IL-25, also called IL-17E, is the only anti-inflammatory cytokine of the IL-17 family, capable of regulating Th17 cells function in autoimmune inflammations. Whether IL-25 affects Th17 cells responses and the development of OB remains poorly understood. Acute rejection (AR) of the lung allograft has been regarded as the main problem for the development of OB, in which infiltrations of monocytes/macrophages play important roles. This study explored the potential role of IL-25 in regulation of macrophages polarization and inhibition of IL-17 production in the progression of OB. Here, we showed that IL-25 directly suppressed the expression of inflammatory cytokines, such as IL-6, IL-23, TNF-α, and IL-1β in LPS-induced pro-inflammatory M1 macrophages in vitro. In vivo data demonstrated that IL-25 deficiency promoted the polarization and function of M1 macrophages and aggravated the progression of OB in murine models of both orthotopic and heterotopic trachea transplantation. In conclusion, these data indicated that IL-25 attenuated OB by suppressing the function of M1 macrophages and IL-17 expression, providing an alternative strategy to intervene the development of OB.
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jie
authors: J
authors: Liu
authors: Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Xiaohui
authors: X
authors: Zhou
authors: Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Zhenzhen
authors: Z
authors: Zhan
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Qingshu
authors: Q
authors: Meng
authors: Department of Pathology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yang
authors: Y
authors: Han
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Qian
authors: Q
authors: Shi
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jiayou
authors: J
authors: Tang
authors: Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jing
authors: J
authors: Li
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: frankfan@tongji.edu.cn.
authors: Huimin
authors: H
authors: Fan
authors: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: zhongmin_liu@sina.com.
authors: Zhongmin
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000166:cytology; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014132:Trachea / Q000637:transplantation*
chemical_list: D007378:Interleukins; C442281:Mydgf protein, mouse
keywords: IL-17; IL-25; Macrophage; Obliterative bronchiolitis; Trachea transplantation