Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium.
Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium; VIB Center for Cancer Biology, VIB, Leuven, Belgium.
Eur Urol Focus. 2022 May;8(3):814-828. doi: 10.1016/j.euf.2021.04.012. Epub 2021 May 4.
Peyronie's disease (PD) is an acquired fibrotic disease affecting the penile tunica albuginea that can lead to curvature and deformities, shortening, and erectile dysfunction. Although immunological mechanisms have been suggested for the pathophysiology of PD, these have not been investigated using single-cell transcriptomics.
To investigate the immunological signature of plaques from PD patients using immunohistochemistry (IHC) and single-cell RNA sequencing (scRNA-Seq).
DESIGN, SETTING, AND PARTICIPANTS: Tunica albuginea biopsy was performed in patients undergoing penile surgery for either PD (n = 12) or plication or penile cancer (control, n = 6). The inclusion criteria for PD patients were stable chronic disease (≥12 mo in duration) and no previous penile surgery or intralesional injection therapy.
IHC was performed on surgical samples from ten patients with PD and five control subjects. An additional two PD and one control sample were used for scRNA-Seq (droplet-based; 10X Genomics). Cell clusters were visualised using heatmaps and t-distributed stochastic neighbour embedding plots (BioTuring v2.7.5).
IHC revealed the presence of myeloid dendritic cells (DCs; CD68, TLR4, CD206), cytotoxic T lymphocytes (CTLs; CD3, CD8), and B lymphocytes (CD20) in PD plaques, which were absent in controls. scRNA-Seq yielded results for 3312 PD and 5658 control cells. Cell clusters contained fibroblasts (COL1A2), myofibroblasts (COL1A2, ACTA2), smooth muscle cells (ACTA2, DES), endothelial cells (VWF), myeloid cells (CD14), T lymphocytes (CD3D), and neutrophils (ALPL). Myeloid cell subclustering showed infiltration of monocyte-derived cells; control tissue contained classical DCs and resident macrophages. Lymphocyte subclustering revealed mucosal-associated invariant T (MAIT) cells and CTLs in PD. Differential gene expression suggests an increase in inflammatory and immune responses in chronic PD. The study is limited by the small scRNA-seq sample size (n = 3) for IHC, mitigated by a larger cohort of historic paraffin-embedded samples (n = 15), which showed largely parallel findings. Owing to tissue stiffness and extracellular matrix adhesion, our single-cell yield was lower for PD than for the control sample.
Our data suggest that even in the chronic PD stage (painless and stable curvature) there is a sustained inflammatory reaction. While vascularisation and collagen production are elevated, the inflammation is driven by specialised monocyte-derived CTL and MAIT cells. These findings could uncover new avenues for medical treatment of PD.
We looked at the role of the immune system in patients suffering from Peyronie's disease, a condition causing shortening and curvature of the penis. We found that even in a stable, chronic stage of the disease, there is activation of the immune system. Our results suggest that there is potential for novel treatments for this condition.
佩罗尼氏病（PD）是一种影响阴茎白膜的获得性纤维性疾病，可导致弯曲和畸形、缩短和勃起功能障碍。尽管已经提出了免疫机制是 PD 病理生理学的原因，但这些原因尚未通过单细胞转录组学进行研究。
使用免疫组织化学（IHC）和单细胞 RNA 测序（scRNA-Seq）研究 PD 患者斑块的免疫特征。
设计、地点和参与者： 在因 PD（n=12）或阴茎成形术或阴茎癌（对照，n=6）而行阴茎手术的患者中进行白膜活检。PD 患者的纳入标准为稳定的慢性疾病（持续时间≥12 个月）和无先前的阴茎手术或病灶内注射治疗。
IHC 对 10 名 PD 患者和 5 名对照患者的手术样本进行了检测。另外两个 PD 和一个对照样本用于 scRNA-Seq（基于液滴的；10X Genomics）。使用热图和 t 分布随机邻域嵌入图（BioTuring v2.7.5）可视化细胞簇。
我们的数据表明，即使在慢性 PD 阶段（无痛和稳定的弯曲），也存在持续的炎症反应。虽然血管生成和胶原蛋白生成增加，但炎症是由专门的单核细胞衍生的 CTL 和 MAIT 细胞驱动的。这些发现可能为 PD 的医学治疗开辟新途径。
我们研究了免疫系统在患有佩罗尼氏病（一种导致阴茎缩短和弯曲的疾病）患者中的作用。我们发现，即使在疾病的稳定、慢性阶段，免疫系统也会被激活。我们的结果表明，这种疾病可能有新的治疗方法。
