Zhou Yao, Deng Xianguang, Ruan Hui, Xue Xing, Hu Zixuan, Gong Jie, Wu Shiting, Liu Lifang
Department of Galactophore, The First Affiliated Hospital of Hunan University of Chinese Medicine, Shaoshan Road, Changsha, 410007, Hunan, China.
Hunan University of Chinese Medicine, Xueshi Road, Changsha, 410208, Hunan, China.
Inflammation. 2025 May 8. doi: 10.1007/s10753-025-02310-8.
Granulomatous mastitis (GM) is a form of non-lactational breast inflammation that is closely associated with autoimmune processes, however its underlying pathogenesis remains elusive. In this study, we employed single-cell RNA sequencing (scRNA-seq) to conduct a comparative analysis of GM lesion tissues versus normal breast tissues, thereby unveiling the immune profile of GM tissues. Our investigation centered on T and NK cells, macrophages, epithelial cells, and endothelial cells. Notably, we observed a substantial infiltration of immune cells in GM tissues, accompanied by immune disorders, an elevation in Th1 cell counts, enrichment of the toll-like receptor (TLR) pathway, and upregulation of various factors including interferon-γ (IFN-γ), C-C motif chemokine ligand 3 (CCL3), CCL4, chemokine (C-X-C motif) ligand (CXCL) 13, CD69, signal transducer and activator of transcription 1 (STAT1), and heat shock protein family A member 1A (HSPA1A). Furthermore, the macrophage subpopulations in GM tissues exhibited a transition to a pro-inflammatory phenotype, enriched for pathways such as interferon-γ (IFN-γ), IFN-α, interleukin-6/janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3), and tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB). Mammary luminal cells demonstrated an impaired estrogenic profile yet displayed upregulation of prolactin downstream signaling pathways, namely the JAK/STAT and mitogen-activated protein kinase (MAPK) pathways. Additionally, vascular endothelial cells were found to recruit immune cells and exhibited a prominent angiogenic profile in GM tissues. Cellular interaction analysis unveiled an intricate network of interactions between mesenchymal and immune cells. This study provides a comprehensive immune landscape of granulomatous mastitis and offers some potential therapeutic targets for the disease.
肉芽肿性乳腺炎（GM）是一种与自身免疫过程密切相关的非哺乳期乳腺炎症，但其潜在的发病机制仍不清楚。在本研究中，我们采用单细胞RNA测序（scRNA-seq）对GM病变组织与正常乳腺组织进行比较分析，从而揭示GM组织的免疫特征。我们的研究集中在T细胞、NK细胞、巨噬细胞、上皮细胞和内皮细胞上。值得注意的是，我们观察到GM组织中有大量免疫细胞浸润，伴有免疫紊乱、Th1细胞计数升高、Toll样受体（TLR）途径富集以及多种因子上调，包括干扰素-γ（IFN-γ）、C-C基序趋化因子配体3（CCL3）、CCL4、趋化因子（C-X-C基序）配体（CXCL）13、CD69、信号转导和转录激活因子1（STAT1）以及热休克蛋白家族A成员1A（HSPA1A）。此外，GM组织中的巨噬细胞亚群表现出向促炎表型的转变，富集了干扰素-γ（IFN-γ）、干扰素-α、白细胞介素-6/Janus激酶/信号转导和转录激活因子3（IL-6/JAK/STAT3）以及肿瘤坏死因子-α/核因子-κB（TNF-α/NF-κB）等途径。乳腺管腔细胞的雌激素特征受损，但催乳素下游信号通路即JAK/STAT和丝裂原活化蛋白激酶（MAPK）通路上调。此外，发现血管内皮细胞在GM组织中募集免疫细胞并表现出显著的血管生成特征。细胞相互作用分析揭示了间充质细胞和免疫细胞之间复杂的相互作用网络。本研究提供了肉芽肿性乳腺炎全面的免疫图谱，并为该疾病提供了一些潜在的治疗靶点。
