Mouse Endometriosis lesion IMC Dataset Lingegowda et al 2024

Endocannabinoids and their receptors modulate endometriosis pathogenesis and immune response (https://doi.org/10.1101/2023.10.11.561929) Endometriosis (EM), characterized by the presence of endometrial-like tissue outside the uterus, is the leading cause of chronic pelvic pain and infertility in females of reproductive age. Despite its high prevalence, the molecular mechanisms underlying EM pathogenesis remain poorly understood. The endocannabinoid system (ECS) is known to influence several cardinal features of this complex disease including pain, vascularization, and overall lesion survival, but the exact mechanisms are not known. Utilizing CNR1 knockout (k/o), CNR2 k/o and wild type (WT) mouse models of EM, we reveal contributions of ECS and these receptors in disease initiation, progression, and immune modulation. Particularly, we identified EM-specific T cell dysfunction in the CNR2 k/o mouse model of EM. We also demonstrate the impact of decidualization- induced changes on ECS components, and the unique disease-associated transcriptional landscape of ECS components in EM. Imaging Mass Cytometry (IMC) analysis revealed distinct features of the microenvironment between CNR1, CNR2, and WT genotypes in the presence or absence of decidualization. This study, for the first time provides an in-depth analysis of the involvement of the ECS in EM pathogenesis and lays the foundation for the development of novel therapeutic interventions to alleviate the burden of this debilitating condition.内源性大麻素及其受体调控子宫内膜异位症的发病机制与免疫应答（https://doi.org/10.1101/2023.10.11.561929） 子宫内膜异位症（Endometriosis, EM）以子宫外出现子宫内膜样组织为特征，是育龄女性慢性盆腔痛与不孕的首要病因。尽管该病患病率较高，但其发病背后的分子机制仍未明确。已知内源性大麻素系统（endocannabinoid system, ECS）可影响该复杂疾病的多项核心特征，包括疼痛、血管生成及病灶整体存活能力，但其具体调控机制仍未阐明。本研究利用子宫内膜异位症小鼠模型，分别为CNR1基因敲除（CNR1 knockout, CNR1 k/o）、CNR2基因敲除（CNR2 knockout, CNR2 k/o）与野生型（wild type, WT）小鼠，揭示了ECS及其两类受体在疾病起始、进展与免疫调控中的作用。尤为重要的是，本研究在CNR2 k/o子宫内膜异位症小鼠模型中发现了疾病特异性T细胞功能异常。本研究还证实了蜕膜化诱导的变化对ECS组分的影响，以及子宫内膜异位症中ECS组分特有的疾病相关转录谱。成像质谱流式细胞术（Imaging Mass Cytometry, IMC）分析显示，在存在或不存在蜕膜化的情况下，不同基因型（CNR1 k/o、CNR2 k/o与WT）小鼠的病灶微环境具有显著差异特征。本研究首次深入解析了ECS在子宫内膜异位症发病机制中的参与作用，为开发新型治疗干预手段以减轻这一致残性疾病的负担奠定了基础。