Th101 - Single Cell Transcriptomic Analysis of Graves’ Disease Thyroid Glands Reveals the Broad Immunoregulatory Potential of Thyrocytes and Stromal Cells: Implications for the Role of Ectopic HLA Class II Expression in Autoimmunity

Daniel Alvarez-Sierra – Postdoctoral fellow, Immunology, IDIVAL, Santander; Ana Marin-Sanchez – Immunology – Hospital Universitario Virgen de las Nieves; Carmela Iglesias – Histopathology – Hospital Universitari Vell d’Hebron; Aroa Gomez-Brey – Transplantation coordination – Vall Hebron Institut de Recerca; Irene Bello – Thoracic Surgery, Transplantation – Hospital Universitari Vall d'Hebron; Enric Caubet – Surgery – Hospital Universitari Vell d’Hebron; Oscar Gonzalez – Surgery – Hospital Universitari Vell d’Hebron; Pablo Moreno – Surgery – Hospital Universitari Bellvitge; Nuria Ruiz – Histopathology – Hospital Universitari Bellvitge; Carles Zafon – Hospital Universitari Vell d’Hebron; Roger Colobran – Immunology – Vall Hebron Institute de Recerca (VHIR)

Abstract Text: The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance. The overexpression of a broad spectrum of immune molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is only moderately expressed by TFCs in autoimmune thyroid indicates that TFCs may actively modulate tolerance. To get a more comprehensive picture of TFC role in regulation, preparations of dispersed TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the described interferon type I and type II signatures and showed unequivocally that TFC express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. However, TFCs either from GD or control glands lack expression of costimulatory molecules CD80/CD86 required for priming T cells. GD fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. This re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC overexpression has been detected in diabetic pancreas.