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

Qian-Yue Zhang, Xiao-Ping Ye (), Zheng Zhou, Chen-Fang Zhu, Rui Li, Ya Fang, Rui-Jia Zhang, Lu Li, Wei Liu, Zheng Wang, Shi-Yang Song, Sang-Yu Lu, Shuang-Xia Zhao, Jian-Nan Lin () and Huai-Dong Song ()
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Qian-Yue Zhang: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Xiao-Ping Ye: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Zheng Zhou: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Chen-Fang Zhu: Shanghai Jiao Tong University
Rui Li: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Ya Fang: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Rui-Jia Zhang: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Lu Li: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Wei Liu: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Zheng Wang: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shi-Yang Song: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Sang-Yu Lu: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shuang-Xia Zhao: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jian-Nan Lin: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Huai-Dong Song: Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28120-2

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