The research team of Professor Song Huaidong of the Ninth Affiliated Hospital found a new pathogenic mechanism and potential therapeutic target of "Hashimoto's thyroiditis"

At 5:00 EST on February 9, 2022, "Nature Communications", a sub-journal of "Nature", published the research paper "Lymphocyte Infiltration and Thyrocyte Destruction is Driven by Stromal" by Professor Song Huaidong's research team from the Ninth People's Hospital affiliated to Shanghai Jiaotong University School of Medicine and Immune Cell Components in Hashimoto's Thyroiditis"
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( https:// ) This study revealed the ectopic infiltration of lymphocytes into thyroid tissue in patients with Hashimoto's thyroiditis, which has long plagued people, leading to the destruction of thyroid follicular cells.

Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease (AITD), with a prevalence of more than 10% in the female population
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Typical HT is characterized by massive lymphocytic infiltration of thyroid tissue, formation of ectopic lymphoid tissue, and destruction of thyroid follicular cells, and the presence of thyroid peroxidase antibody (TPOAb) and thyroglobulin Antibodies (Thyroglobulin antibody, TGAb), but so far, the mechanism leading to massive lymphocytic infiltration and thyroid cell destruction in the thyroid tissue of HT patients is poorly understood

Figure 1.
Multicolor immunofluorescence staining of thyroid tissue sections from patients with Hashimoto's thyroiditis showing the distribution of CCL21+ stromal cells

The pathogenesis of HT is unclear and there is a lack of treatment for the cause
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To further explore the pathogenesis of HT, Song Huaidong's group identified multiple subpopulations of thyroid tissue stromal cells in HT patients by single-cell sequencing, among which CCL21+ myofibroblasts and CCL21+ positive fibroblasts both highly expressed CCL19 and CCL21

Figure 2.
There are specific inflammatory macrophages and inflammatory dendritic cell subsets with high IL-1β expression in the thyroid tissue of patients with Hashimoto's thyroiditis

In addition, the study also found that there are inflammatory macrophages and dendritic cell subsets specifically in the thyroid tissue of patients with Hashimoto's thyroiditis, and they all significantly overexpress a number of inflammation-related genes.
The expression increased most significantly
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Previous literature has shown that IL-1β can promote CD40L-mediated dendritic cell activation, promote the activation and proliferation of CD4+ T cells stimulated by antigens, promote Th17 cell differentiation, and induce ectopic high expression of FAS in thyroid follicular cells, thereby making Apoptotic destruction of thyroid follicular cells

This study suggests that CCL19/CCL21 may play an important role in the infiltration of immune cells in thyroid tissue and the formation of tertiary lymphoid tissue during the occurrence of HT, while specific inflammatory macrophages and dendritic cells infiltrated into thyroid tissue A subpopulation that may contribute to the destruction of thyroid follicles by secreting IL-1β
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Therefore, targeted blocking of the interaction between CCL19/CCL21 and CCR7 is expected to block thyroid immune cell infiltration, thereby reducing thyroid follicle destruction and delaying the onset of hypothyroidism

In the past ten years, only 8 papers have been published in the international famous journal CNS and its sub-journals in the field of global autoimmune thyroid disease research
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This is the second research paper on the pathogenesis of autoimmune thyroid disease published by Professor Song Huaidong's team in the CNS sub-journal after a lapse of 10 years.

Song Huaidong is an academic leader, doctoral tutor, second-level professor, chief physician, researcher, and second-instance expert of the National Foundation of China, Ninth People's Hospital affiliated to Shanghai Jiaotong University School of Medicine
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Top Ten Outstanding Young People in Shanghai, Special Allowance Expert of the State Council, National Talent of "New Century Talent Project" of Ministry of Personnel, "New Century Talent" of Ministry of Education, Shanghai Excellent Discipline Leader, and Shanghai "Leading Talent"