2. Academic Validation
  3. Single-Cell RNA Sequencing of Thyroid Tissues Reveals Pathogenesis of Graves' Disease

Single-Cell RNA Sequencing of Thyroid Tissues Reveals Pathogenesis of Graves' Disease

  • Adv Sci (Weinh). 2026 Jan;13(1):e08449. doi: 10.1002/advs.202508449.
Xiaoyi Zhou 1 2,  Jia Cong 1 2,  Rongguang Peng 1 2,  Dichen Yang 1 2,  Chenchen Dong 1 2,  Jing Xie 3,  Jiqi Yan 4,  Jie Kuang 4,  Fubin Li 5,  Leng Siew Yeap 5,  Xiaoyan Xie 1 2,  Haolong Yin 1 2,  Rulai Han 1 2,  Liyun Shen 1 2,  Yulin Zhou 1 2,  Guang Ning 1 2,  Shu Wang 1 2,  Weiqing Wang 1 2,  Lei Ye 1 2
Affiliations

Affiliations

  • 1 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200023, China.
  • 2 Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, SJTUSM, Shanghai, 200023, China.
  • 3 Department of Pathology, Ruijin Hospital, SJTUSM, Shanghai, 200025, China.
  • 4 Department of General Surgery, Ruijin Hospital, SJTUSM, Shanghai, 200025, China.
  • 5 Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, SJTUSM, Shanghai, 200025, China.
PMID: 41126733 DOI: 10.1002/advs.202508449
Abstract

Graves' disease (GD) is an autoimmune disorder primarily targeting the thyroid tissue. While major histocompatibility complex (MHC)-dependent B cell activation and thyroid-stimulating hormone receptor (TSHR) autoantibody production are central to GD, the intrathyroidal immune landscape remains largely unexplored. Through single-cell RNA Sequencing (scRNA-seq), this work constructed a comprehensive immune cell atlas, revealing dominant IFN-γ-secreting CD4+ T cells, expanded T peripheral helper (Tph) cells, CD11c+ atypical B cells, and CD8+ effector T cells. Notably, stress-surveilling γδ T/NK cells are enriched in GD. Thyroid follicular cells (TFCs) in GD exhibited a stressed phenotype, and in vitro functional assays showed that they promote γδ T cell activation and proliferation. γδ T cells may recruit conventional type 1 dendritic cells (cDC1) via XCL1/XCL2, suggesting a potential link to adaptive immune reorganization. These findings suggest an additional MHC-independent pathway linking TFC stress to autoimmune activation via γδ T cells in GD pathogenesis.

Keywords

Tph cells; graves’ disease; immune cell atlas; single‐cell RNA sequencing; stress surveillance; γδ T Cells.

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