Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Medical Immunology, Chiba University Graduate School of Medicine, Chiba, Japan.
PLoS One. 2020 May 8;15(5):e0232884. doi: 10.1371/journal.pone.0232884. eCollection 2020.
Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis.
Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs).
A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs.
Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.
在肺移植过程中小组织相容性抗原（mHA）差异会导致闭塞性细支气管炎（OB）。本研究通过微阵列分析评估了小鼠原位肺移植模型中的基因表达。
从 C57BL/10（H-2b）供体小鼠的左肺移植到 mHA 错配的 C57BL/6（H-2b）受体小鼠中。通过病理确认并分析了三组（OB、非 OB 和假对照）。通过微阵列和免疫组织化学染色确定肺移植物中的基因表达变化，并通过定量 PCR 在肺和纵隔淋巴结（LN）中验证基因。
与 sham 组相比，OB 肺中的 1343 个基因上调。与先天免疫相关的基因，如 TLR2 和 CCL3，以及与适应性免疫相关的基因，如 H2-ab1 和 IL-21，表达显著上调。在 OB 支气管上皮中观察到 MHC Ⅱ类抗原的阳性标记，同时伴有 B 细胞。我们发现 OB 肺中 TLR2、CCL3、H2-ab1、IL-21、IGHG3、IFNG 和 PDCD1mRNA 表达增加，OB LN 中 IL-21、IGHG3 和 PDCD1 表达增加。
适应性和先天免疫反应参与了肺移植后的 OB，相关基因的遗传检查可用于 OB 的检测。
