Innate immune activation and thyroid autoimmunity

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Activation of innate and acquired immune responses, which can be induced by infection, inflammation or tissue injury, may impact the development of autoimmunity. Using cultured thyroid cells, we show that cell injury prompts the release of genomic DNA into the cytosol, which is associated with the production of type I interferons(IFNs), inflammatory cytokines and chemokines. Molecules necessary for antigen processing and presentation to lymphocytes are also induced in thyroid cells by injury. In order to identify molecules responsible for sensing cytosolic dsDNA, we directly identified the cellular proteins that bound a dsDNA sepharose column by mass spectrometry. Our analysis identified genomic DNA fragments released by cell injury are recognized by extrachromosomal histone H2B, which results in the activation of genes involved in both innate and acquired immune responses in thyroid cells and suppression of thyroid function.