Immune landscape in NOD.H-2h4 mouse model thyroid revealed by single-cell RNA sequencing.

Abstract

BACKGROUND: Hashimoto's thyroiditis is a common autoimmune disorder characterized by lymphocytic infiltration and thyroid follicular cell destruction, leading to permanent hypothyroidism and an increased, clinically risk of thyroid malignancy. However, the specific roles of each thyroidal cell types participating the immune dysregulation of HT remain incompletely elucidated. METHODS: We performed single-cell RNA sequencing on thyroid tissues from NOD.H-2h4 mice at three disease stages (4, 8, and 16 weeks). A total of 38,461 cells were analyzed to characterize the transcriptomic profiles of twelve distinct populations, comprising immune infiltrates and resident tissue cells. RESULTS: Our single-cell atlas revealed a downregulation of Nkx2-1, suggesting a potential loss of thyrocyte identity and function. Inferred intercellular communication predicted that thyrocytes and stromal cells might interact with immune cells via the putative App-Cd74 axis. Tregs displayed transcriptional signatures of dysfunction and instability. Furthermore, the transcriptomic landscape indicated that chronic stress potentially induces thyrocytes into inflammatory and antigen-presenting phenotypes. Collectively, our single-cell transcriptomic insights highlight thyrocyte plasticity and Treg dysfunction as potential drivers of disease progression. CONCLUSION: We constructed a single-cell transcriptomic atlas of the NOD.H-2h4 mouse model. This work provides a dataset for further research into the cellular mechanisms of Hashimoto's thyroiditis.