Innate immune activation and thyroid autoimmunity

先天性和获得性免疫应答的激活（其可由感染、炎症或组织损伤诱导）可影响自身免疫的发展。使用培养的甲状腺细胞，我们表明，细胞损伤促使基因组DNA释放到胞质溶胶中，这与I型干扰素（IFN），炎症细胞因子和趋化因子的产生有关。抗原加工和呈递给淋巴细胞所必需的分子也在甲状腺细胞中因损伤而被诱导。为了鉴定负责感测胞质dsDNA的分子，我们通过质谱法直接鉴定结合dsDNA琼脂糖柱的细胞蛋白。我们的分析确定了细胞损伤释放的基因组DNA片段被染色体外组蛋白H2B识别，这导致甲状腺细胞中参与先天性和获得性免疫应答的基因活化和甲状腺功能抑制。

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.