Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
BMC Pulm Med. 2024 Aug 13;24(1):392. doi: 10.1186/s12890-024-03207-2.
The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques.
Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis).
NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased.
NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.
非结核分枝杆菌肺病（NTM-PD）的免疫学特征在很大程度上尚不清楚。本研究使用数字空间分析技术研究了 NTM-PD 的免疫学特征。
本研究纳入了 2006 年 1 月 1 日至 2020 年 12 月 31 日期间在首尔国立大学医院就诊的 6 例 NTM-PD 患者的肺组织标本，进行 RNA 测序。对支气管周围区域的组织芯进行 CD3、CD68 和 DNASyto13 染色，并通过 PCR 扩增和 Illumina 测序定量全转录组水平的基因表达。同时纳入了同期收集的 6 例支气管扩张症患者的肺组织作为对照。使用免疫组化（IHC）在另一队列（30 例 NTM-PD 患者和 15 例支气管扩张症患者）中验证了 RNA 测序结果。
NTM-PD 在 T 细胞和巨噬细胞中表现出明显不同的基因表达模式。基因集富集分析显示，与抗原呈递和加工相关的途径在 NTM-PD 中上调，尤其是在巨噬细胞中。巨噬细胞更为普遍，与 M1 表型相关的基因（CD40 和 CD80）的表达显著升高。尽管 NTM-PD 组的巨噬细胞被激活，但 T 细胞活性并未改变。值得注意的是，NTM-PD 中协同刺激分子 CD28 的表达降低。IHC 分析显示，表达 Foxp3 或 TIM-3 的 T 细胞增加，这些细胞促进 T 细胞的调节功能。
NTM-PD 表现出独特的免疫学特征，表现为巨噬细胞激活而 T 细胞未激活。
