title: Anti-IL-23 antibody blockade of IL-23/IL-17 pathway attenuates airway obliteration in rat orthotopic tracheal transplantation.
abstract: Obliterative bronchiolitis (OB) has been a major obstacle to long-term allograft survival after lung transplantation, and the underlying mechanism is not well understood. As IL-23/IL-17 pathway has been shown to play important roles in airway inflammation, in this study we have investigated the role of IL-23/IL-17 pathway in acute and chronic airway allograft rejection. We used a rat OB model in orthotopic tracheal transplantation, and investigated the effects of anti-IL-23 blockade antibody on acute and chronic airway allograft rejection. Anti-IL-23 antibody impaired the function of IL-23 in inducing IL-17 production. The rats that received allografts and treated with anti-IL-23 antibody showed significantly less symptom of airway obliteration and chronic transplant rejection compared with control rats which received physiological saline or IgG antibody. Taken together, our results suggest that anti-IL-23 antibody is effective in protecting allograft rejection and the development of chronic OB in allo-tracheal transplantation. These findings may have implications for new therapies to prevent OB and allograft rejection in human lung transplantation.
authors.affiliation: Dept of Cardio-Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cao
authors.forename: Qin
authors.initials: Q
authors.lastname: Lan
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Guangliang
authors.initials: G
authors.lastname: Tang
authors.forename: Chenli
authors.initials: C
authors.lastname: Qiu
authors.forename: Chao
authors.initials: C
authors.lastname: Qiu
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000402:Airway Obstruction; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002478:Cells, Cultured; D002908:Chronic Disease; D018450:Disease Progression; D006084:Graft Rejection / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016377:Organ Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014132:Trachea / Q000637:transplantation*
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D053759:Interleukin-23