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

## TL;DR

This study uses single-cell RNA sequencing to uncover immune cell changes in thyroid tissues of Graves' disease patients, revealing new pathways in the disease's progression.

## Contribution

The study identifies an MHC-independent pathway involving γδ T cells and stressed thyroid follicular cells in Graves' disease pathogenesis.

## Key findings

- GD thyroid tissues show enrichment of IFN-γ-secreting CD4+ T cells, Tph cells, and CD11c+ B cells.
- Stressed thyroid follicular cells activate γδ T/NK cells, which recruit cDC1 cells.
- γδ T cells may link TFC stress to autoimmune activation in GD.

## 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.

Using single‐cell RNA sequencing and TCR profiling, this study constructed an immune cell atlas in thyroid tissue of Graves’ disease (GD), revealing dominant IFN‐γ‐secreting CD4+ T cells, expanded Tph and CD11c+ B cells, and enriched T/NK cells. Notably, GD thyroid follicular cells (TFCs) activated γδ T cells, which recruited cDC1 cells, suggesting a mechanism linking TFC stress to autoimmune activation in GD pathogenesis.