title: HMGB1 is involved in chronic rejection of cardiac allograft via promoting inflammatory-like mDCs.
abstract: Chronic rejection that leads to diffuse narrowing and occlusion of graft vessels is the most important cause of morbidity and mortality following cardiac transplantation. The role and underlying mechanism of high-mobility group box 1 (HMGB1), as an established inflammatory mediator in acute rejection, remains poorly understood in chronic rejection. Here, we assessed the effects and mechanisms of HMGB1 on the chronic rejection using single MHC Class II-mismatched mouse cardiac transplantation model. It was found that HMGB1 was increased accompanying with the development of chronic rejection, while blockade of HMGB1 with specific neutralizing mAb substantially ameliorated chronic rejection-mediated vasculopathy and fibrosis of allograft, as well as markedly decreased T cell infiltration and production of IL-17A and interferon-gamma in allograft and recipient's spleen. Further, anti-HMGB1 antibody treatment significantly declined the number and frequency of mature dendritic cells (DCs) in allograft and recipient's spleen, especially CD11b(+) Ly6C(high) matured DCs that share the phenotypes with inflammatory-DCs. These findings indicate that HMGB1 contributes to chronic rejection, and HMGB1 blockade may be a novel mean to disrupt the proinflammatory loop after heart transplantation.
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, China; Key Laboratory of Organ Transplantation, Ministry of Public Health, China.
authors.forename: H
authors.initials: H
authors.lastname: Zou
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Gao
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Ming
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Xiong
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Fang
authors.forename: Z
authors.initials: Z
authors.lastname: Tan
authors.forename: F
authors.initials: F
authors.lastname: Gong
authors.forename: F
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005355:Fibrosis; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D024243:HMGB1 Protein / Q000235:genetics / Q000502:physiology*; D006333:Heart Failure / Q000276:immunology; D016027:Heart Transplantation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014184:Transplantation, Homologous
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: Cardiac allograft; DC; HMGB1; IFN-γ; IL-17A; chronic rejection