Mesh : Humans Graves Disease / pathology immunology genetics metabolism Thyroid Gland / pathology metabolism Hashimoto Disease / pathology immunology metabolism genetics Antigens, Differentiation, B-Lymphocyte / metabolism genetics Fibroblasts / metabolism pathology Histocompatibility Antigens Class II / metabolism genetics Thyroid Epithelial Cells / metabolism pathology Endothelial Cells / metabolism pathology Transcriptome Myofibroblasts / metabolism pathology Stromal Cells / metabolism pathology Female Macrophage Migration-Inhibitory Factors Intramolecular Oxidoreductases

来  源:   DOI:10.1038/s41467-024-50192-5   PDF(Pubmed)

Abstract:
Autoimmune thyroid diseases (AITD) such as Graves\' disease (GD) or Hashimoto\'s thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF+ myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD.
摘要:
自身免疫性甲状腺疾病(AITD),如Graves病(GD)或桥本甲状腺炎(HT)是器官特异性疾病,涉及甲状腺组织不同成分之间的复杂相互作用。这里,我们使用空间转录组学来探索分子结构,甲状腺组织中存在的不同细胞的异质性和位置,包括甲状腺滤泡细胞(TFC),基质细胞如成纤维细胞,内皮细胞,和甲状腺浸润淋巴细胞.我们鉴定了AITD患者甲状腺样品中CD74和MIF表达上调的受损抗原呈递TFC。此外,我们发现结缔组织中两个主要的成纤维细胞亚群,包括ADIRF+肌成纤维细胞,主要富集在GD,和炎性成纤维细胞,富含HT患者。我们还证明了AITD中开窗PLVAP+血管的增加,尤其是在GD。我们的数据揭示了可能在AITD的发病机理中起作用的基质和甲状腺上皮细胞亚群。
公众号