Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Department of geriatric endocrinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
Nat Commun. 2022 Feb 9;13(1):775. doi: 10.1038/s41467-022-28120-2.
Hashimoto's thyroiditis (HT) is the most common autoimmune disease characterized by lymphocytic infiltration and thyrocyte destruction. Dissection of the interaction between the thyroidal stromal microenvironment and the infiltrating immune cells might lead to a better understanding of HT pathogenesis. Here we show, using single-cell RNA-sequencing, that three thyroidal stromal cell subsets, ACKR1 endothelial cells and CCL21 myofibroblasts and CCL21 fibroblasts, contribute to the thyroidal tissue microenvironment in HT. These cell types occupy distinct histological locations within the thyroid gland. Our experiments suggest that they might facilitate lymphocyte trafficking from the blood to thyroid tissues, and T cell zone CCL21 fibroblasts may also promote the formation of tertiary lymphoid organs characteristic to HT. Our study also demonstrates the presence of inflammatory macrophages and dendritic cells expressing high levels of IL-1β in the thyroid, which may contribute to thyrocyte destruction in HT patients. Our findings thus provide a deeper insight into the cellular interactions that might prompt the pathogenesis of HT.
桥本甲状腺炎（HT）是最常见的自身免疫性疾病，其特征为淋巴细胞浸润和甲状腺细胞破坏。剖析甲状腺间质微环境与浸润免疫细胞之间的相互作用，可能有助于更好地理解 HT 的发病机制。在这里，我们使用单细胞 RNA 测序技术表明，三种甲状腺间质细胞亚群，ACKR1 内皮细胞以及 CCL21 肌成纤维细胞和 CCL21 成纤维细胞，有助于 HT 中的甲状腺组织微环境。这些细胞类型在甲状腺中占据不同的组织学位置。我们的实验表明，它们可能有助于淋巴细胞从血液迁移到甲状腺组织，并且 T 细胞区 CCL21 成纤维细胞也可能促进 HT 特征性的三级淋巴器官的形成。我们的研究还表明，甲状腺中存在表达高水平 IL-1β 的炎症性巨噬细胞和树突状细胞，这可能导致 HT 患者的甲状腺细胞破坏。因此，我们的研究结果更深入地了解了可能促使 HT 发病的细胞相互作用。
