The impact of locally produced anti-donor specific antibody in de novo intrapulmonary lymphoid tissue on RAS, the sever form of chronic rejection after lung transplantation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: The University of Tokyo (2015-2016); Kyoto University (2014)
• Principal Investigator: Sato Masaaki 東京大学, 医学部附属病院, 講師 (00623109)
• Co-Investigator(Kenkyū-buntansha): 毛受 暁史 京都大学, 医学(系)研究科(研究院), 助教 (30527081) ; 青山 晃博 京都大学, 医学(系)研究科(研究院), 助教 (60379047)
• Research Collaborator: MIYAMOTO Ei ; TAKAHAGI Akihiro ; KAWASHIMA Mitsuaki
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺移植 / 慢性拒絶 / RAS / BOS / リンパ組織新生 / 抗ドナー特異抗体 / 抗体関連拒絶

Outline of Final Research Achievements

Among chronic rejection after lung transplantation, the severe form, restrictive allograft syndrome (RAS) was proposed by the principle investigator (Sato M) in 2010. Regarding the mechanisms, we hypothesized that the lung exposed to multiple external stimuli through ambient air becomes a lymphoid organ. In a RAS model using orthotopic rat lung transplantation, we demonstrated intra-pulmonary formation of lymphoid tissue formation associated with local production of anti-donor-specific antibodies. Such antibody-mediated process was found to be important in RAS, whereas in the conventional form of chronic rejection in which the airway is mainly affected, an airway-centered inflammatory process such as chronic infection was found to be important. We further utilized an orthotopic mouse tracheal transplant model and then demonstrated that airway-centered inflammation not only induces rejection but also directly activates fibroblasts by signaling through a toll-like receptor.

Free Research Field

呼吸器外科