Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions
Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions
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DOI：
10.1089/thy.2011.0480
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发表时间：
2013-04-01
期刊：
影响因子：
6.6
通讯作者：
Suzuki, Koichi
中科院分区：
文献类型：
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作者：
Kawashima, Akira;Yamazaki, Kazuko;Suzuki, Koichi
背景资料：自身免疫性甲状腺疾病是一种典型的器官特异性自身免疫性疾病，其特征在于甲状腺自身抗体的产生和淋巴细胞浸润到甲状腺中。然而，特异性甲状腺抗体产生的潜在机制在很大程度上是未知的。最近的研究表明，先天免疫反应影响自身免疫反应的表型和严重程度。此外，似乎即使是非免疫细胞，包括甲状腺细胞，也有能力发起这种反应。本研究的目的是对甲状腺在各种“非自身”和“自身”因素刺激下的先天免疫反应进行更详细的分析，这些因素可能有助于引发自身免疫反应。我们使用大鼠甲状腺FRTL-5细胞、人甲状腺细胞和小鼠来研究各种病原体相关分子模式（PAMP）、甲状腺相关分子模式（DAMP）、结果：RT-PCR分析显示，大鼠和人甲状腺细胞均表达Toll样受体（Toll like receptor，TLR）mRNA，Toll样受体可检测PAMPs。用TLR配体刺激甲状腺细胞导致干扰素-β（IFN-β）启动子和活化B细胞的核因子κ-轻链增强子（NF κ B）依赖性启动子活化。结果，产生了促炎细胞因子、趋化因子和I型干扰素。当用双链DNA刺激甲状腺细胞时，观察到类似的激活，这是典型的DAMP之一。除了这些PAMPs和DAMPs，治疗甲状腺细胞高浓度的碘化物增加各种cytokines.Conclusion mRNA的表达：我们表明，甲状腺细胞表达功能传感器的外源性和内源性的危险，他们能够启动先天性免疫反应，而无需免疫细胞的协助。这种反应可能与甲状腺炎的发展有关，而甲状腺炎又可能引发自身免疫反应。
Background: Autoimmune thyroid disease is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. However, the underlying mechanisms by which specific thyroid antibodies are produced are largely unknown. Recent studies have shown that innate immune responses affect both the phenotype and the severity of autoimmune reactions. Moreover, it appears that even non-immune cells, including thyroid cells, have an ability to launch such responses. The aim of this study was to conduct a more detailed analysis of innate immune responses of the thyroid upon stimulation with various "non-self" and "self" factors that might contribute to the initiation of autoimmune reactions.Methods: We used rat thyroid FRTL-5 cells, human thyroid cells, and mice to investigate the effects of various pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and iodide on gene expression and function that were related to innate immune responses.Results: RT-PCR analysis showed that both rat and human thyroid cells expressed mRNAs for Toll-like receptors (TLRs) that sense PAMPs. Stimulation of thyrocytes with TLR ligands resulted in activation of the interferon-beta (IFN-beta) promoter and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappa B)-dependent promoter. As a result, pro-inflammatory cytokines, chemokines, and type I interferons were produced. Similar activation was observed when thyroid cells were stimulated with double-stranded DNA, one of the typical DAMPs. In addition to these PAMPs and DAMPs, treatment of thyroid cells with high concentrations of iodide increased mRNA expression of various cytokines.Conclusion: We show that thyroid cells express functional sensors for exogenous and endogenous dangers, and that they are capable of launching innate immune responses without the assistance of immune cells. Such responses may relate to the development of thyroiditis, which in turn may trigger autoimmune reactions.