IL-17A is implicated in the pathogenesis of chronic lung allograft dysfunction, which limits survival after lung transplantation. While many cells express the IL-17 receptor A (IL-17RA) which is the main receptor for IL-17A, the cellular targets of IL-17A in development of post-transplant fibrosis are unknown. The purpose of this study was to determine whether IL-17RA expression by donor or recipient structural or bone marrow (BM) cells is required for the development of allograft fibrosis in a mouse intrapulmonary tracheal transplantation (IPTT) model. BM chimeras were generated using C57BL/6 and IL-17RA-knockout mice. After engraftment, allogeneic IPTTs were performed using the chimeric and BALB/c mice as donors or recipients. This allowed us to assess the effect of IL-17RA deficiency in recipient BM, recipient structural, donor BM, or donor structural compartments separately. Tracheal grafts, the surrounding lung, and mediastinal lymph nodes were assessed 28 days after IPTT. Only recipient BM IL-17RA deficiency resulted in attenuation of tracheal graft obliteration. In the setting of recipient BM IL-17RA deficiency, T cells and neutrophils were decreased in mediastinal lymph nodes. Additionally, recipient BM IL-17RA deficiency was associated with increased B220⁺PNAd⁺ lymphoid aggregates, consistent with tertiary lymphoid organs, in proximity to the tracheal allograft. In this IPTT model, recipient BM-derived cells appear to be the primary targets of IL-17RA signaling during fibrotic obliteration of the tracheal allograft.

IL-17A 与慢性同种异体肺移植功能障碍的发病机制有关，这限制了肺移植后的存活。虽然许多细胞表达 IL-17 受体 A (IL-17RA)，它是 IL-17A 的主要受体，但 IL-17A 在移植后纤维化发展中的细胞靶点尚不清楚。本研究的目的是确定小鼠肺内气管移植 (IPTT) 模型中同种异体移植纤维化的发展是否需要供体或受体结构或骨髓 (BM) 细胞表达 IL-17RA。使用 C57BL/6 和 IL-17RA 敲除小鼠产生 BM 嵌合体。植入后，使用嵌合和 BALB/c 小鼠作为供体或受体进行同种异体 IPTT。这使我们能够评估 IL-17RA 缺乏对受体 BM、受体结构、供体 BM 的影响，或供体结构隔室分开。在 IPTT 后 28 天评估气管移植物、周围肺和纵隔淋巴结。只有受体 BM IL-17RA 缺乏导致气管移植物闭塞减弱。在受体 BM IL-17RA 缺乏的情况下，纵隔淋巴结中的 T 细胞和中性粒细胞减少。此外，受体 BM IL-17RA 缺乏与 B220 增加有关⁺ PNAd ⁺淋巴聚集物，与三级淋巴器官一致，靠近同种异体气管。在该 IPTT 模型中，受体 BM 衍生细胞似乎是同种异体气管移植物纤维化闭塞期间 IL-17RA 信号传导的主要目标。