Endocrine Abstracts

Introduction: Autoimmune thyroid diseases (AITD) such as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT) are autoimmune, organ-specific diseases probably related to a complex and multifactorial interplay of specific susceptibility genes and environmental exposures. T lymphocytes and their secretory cytokines play indispensable roles in disrupting tolerance. However, their roles are often complex and full of interactions among distinct components of the thyroid ecosystem. Novel technologies such as spatial transcriptomics (ST), allow us to explore the molecular architecture and the heterogeneity and landscape of the different cell-states within tissues.

Methodology: We profiled 8 human thyroid samples (3 HT, 3 GD and 2 controls) samples by ST using the Visium Spatial Gene Expression platform (10× Genomics). We spatially localized and histologically annotated thyroid folicular cells (TFCs), connective tissue and vessel areas to be independently studied. Furthermore, we defined and mapped into the space disease-associated subpopulations of cells. These markers have been validated using public single cell data and by protein in situ detection with immunofluorescence (IF) and/or immunohistochemistry (IHC).

Results: We revealed damaged antigen-presenting TFCs located close to the immune infiltration that contributed to the autoperpetuation of the immune response in AITD. Interestingly, we reported the participation of different fibroblasts subpopulations in HT and GD patients. Specifically, GD-associated ADIRF+ myofibroblasts surrounding TFCs and inflammation-associated fibroblasts (IAFs) within the connective tissue of HT patients. Furthermore, the presence of fenestrated PLVAP+ vessels in AITD, especially in GD, was highlighted.

Conclusions: Our data provides the molecular and cellular heterogeneity of AITD microenvironment and points toward the importance of different novel markers associated to cell subpopulations in the stroma and thyroid epithelium that could be essential to understand the pathogenesis of AITD.