Changes in gene expression profile and development of autoimmunity in the thyroid following infection.

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Pathological basis of autoimmune thyroid diseases are still largely unknown. Although it has been suggested that infection and/or tissue damage precede the onset of autoimmunity, the relationship between such incidences and the triggering of autoimmune reactions was not clear. In the present study, we have shown that double-stranded (ds) DNA released from pathogen or host genome acts on thyroid cells to produce type I interferons, proinflammatory cytokines and chemokines as well as major histocompatibility complex (MHC) and related molecules necessary for antigen processing and presentation. This effect was dsDNA-specific and independent of toll-like receptors (TLRs) or RIG-I, known cellular receptors for pathogen-associated molecular patterns (PAMPs). We separately showed that conventional TLR-dependent pathways are also operating in the thyroid and involved in the initiation of innate immune reaction. TLRs are indeed expressed in the thyroid follicular epithelium and in mast cells in the gland. Interestingly, stimulation of thyroid cells by dsDNA or TLR ligands not only activated innate immune reactions, but resulted in suppression of iodide uptake and hormone synthesis of the thyroid, which is corresponding to the thyroid dysfunction seen in the prodromal period of viral infection and non-thyroid illness. These evidence suggest that infection and/or tissue damage can activate innate immunity in the thyroid and enhance the adjuvant effect, which may trigger autoimmune reactions. Additionally, such events may be a direct cause of thyroid dysfunction.