期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 178, 期 4, 页码 379-388出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200711-1648OC
关键词
idiopathic pneumonia syndrome; graft-versus-host disease; CD4 T cells; IL-17; antigen-presenting cells
资金
- Swiss Life Jubilaumsstiftung
Rationale: Pulmonary complications of hematopoietic stem cell transplantation include infections and graft-versus-host diseases, such as idiopathic pneumonia syndrome (IPS). Conflicting data exist regarding the role of the interferon (IFIN)-gamma-producing Th1 CD4(+) T-cell subset and IL-17A in IPS. Objectives: To determine the role of IFN-gamma and IL-17A in the establishment of pulmonary graft-versus-host disease. Methods: A semiallogeneic murine model based on C57BL/6 x BALB/c as recipients with transplantation of BALIB/cRAG2(-/-) bone marrow and transfer of different genetic knockout T cells (T-bet(-/-), IFN-gamma(-/-), IFN-gamma R(-/-)) on a BALIB/c background. Lung tissue was examined for parenchymal changes and infiltrating cells by histology and fluorescence-activated cell sorter analysis. Measurements and Main Results: After transfer of semiallogeneic bone marrow together with donor CD4(+) T cells lacking IFN-gamma or T-bet-a T-box transcription factor controlling Th1 commitment-we found severe inflammation in the lungs, but no enhancement in other organs. In contrast, wild-type donor CD4(+) T cells mediated minimal inflammation only, and donor CD8(+) T cells were not required for IPS development. Mechanistically, the absence of IFN-gamma or IFN-gamma signaling in pulmonary parenchymal cells promoted expansion of IL-17A-producing CD4(+) T cells and local IL-17A release. In vivo depletion of IL-17A reduced disease severity. Conclusions: One mechanism of IFN-gamma protection against IPS is negative regulation of the expansion of pathogenic IL-17A-producing CD4(+) T cells through interaction with the IFN-gamma receptor on the pulmonary parenchymal cell population.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据