MON-425 Defining Disease-Specific Epithelial Cell Phenotypes in Thyroid Autoimmunity

Abstract Disclosure: M. Song: None. E. Biederstedt: None. E.E. Rodriguez: None. V. Digania: None. E. Koelliker: None. S. Parangi: None. M. Rengarajan: None. The thyroid gland offers an ideal model to study tissue-specific autoimmunity directly in humans. The thyroid is susceptible to autoimmune attack by both cellular and humoral immunity, exemplified by Hashimoto’s thyroiditis and Graves Disease, respectively. These two diseases are characterized by markedly different clinical presentations and antigenic triggers, but we and others have found that both are characterized by the emergence of a population of thyrocytes that ectopically express major histocompatibility complex class II (MHCII). MHCII is normally expressed by antigen-presenting cells, such as B cells and myeloid cells, and is not expressed in thyrocytes at baseline. In previously presented work from our lab, we found that MHCIIpos thyrocytes express genes suggestive of immune-modulation. Here we aim to better characterize MHCIIpos thyrocytes to understand how they may modulate their local thyroid environment during autoimmune disease. We have developed an approach to selectively isolate MHCIIpos and MHCIIneg thyrocytes from surgical thyroid specimens from patients with Hashimoto’s thyroiditis (n = 3) or Graves disease (n=3). We performed bulk RNA sequencing on these samples and confirmed upregulation of multiple components of the MHCII apparatus in MHCIIpos but not MHCIIneg thyrocytes. Strikingly, MHCIIpos cells exhibited a substantially different transcriptional phenotype, including up-regulation of complement factors and other immune-modulatory genes. We have additionally developed methods to isolate specific pathogenic T-cell populations in the thyroid that our lab previously identified. We are currently examining whether MHCIIpos phenotype is associated with changes in pathogenic T-cell state in the thyroid in Hashimoto’s thyroiditis and Graves disease. Presentation: Monday, July 14, 2025