Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto’s thyroiditis

Abstract

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.

A clinical and molecular pathology prediction model for central lymph node metastasis in cN0 papillary thyroid microcarcinoma

“…HT is characterized by enrichment of inflammatory factors, also known as autoimmune thyroiditis. It produces a significant amount of lymphocytes and macrophages, both of which naturally possess antitumor activity, and the autoimmune antibodies released by HT-related lymphocytes can also destroy the follicles, contributing to their shrinkage and fibrosis ( 22 , 23 ). Therefore, PTC tissues with HT usually exhibit a microscopic fibrous cell layer wrapping around the primary lesion, indicating that the combination of HL has a limiting effect on the progression of the primary lesion, which can significantly impede the spread and infiltration of tumor cells ( 24 ), reduce the invasiveness of the primary lesion ( 25 ), and decrease CLNM chance ( 26 ).…”

Single-cell transcriptomic analysis revealed the tumor-associated microenvironment of papillary thyroid carcinoma with metastasis

“…In the PTC tumors, we identi ed a similar TAM subtype with high phagocytosis and high oxidative phosphorylation signature. Recently, distinct clusters of DC cells were identi ed in HCC, lung cancer, neck squamous cell carcinoma [38], and non-malignant in amed tissue [39].…”

FAP‐α+ immunofibroblasts in oral lichen planus promote CD4+ T‐cell infiltration via CCL5 secretion

“…32 CCL21 + fibroblasts may promote the formation of tertiary lymphoid organs characteristic of Hashimoto's thyroiditis. 33 However, there are few studies on the effects of OLP fibroblasts. T cell-mediated immune disorders involve various cytokines, among which chemokines play an important role in the pathogenesis of OLP.…”

“…In vitiligo, fibroblasts recruit T cells through CXCL9 and CXCL10 32 . CCL21 + fibroblasts may promote the formation of tertiary lymphoid organs characteristic of Hashimoto's thyroiditis 33 . However, there are few studies on the effects of OLP fibroblasts.…”