PDF(Pubmed)
Abstract：
The process of thyroid autoimmunization develops against the background of genetic predispositions associated with class II human leukocyte antigens (HLA-DR), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and forkhead transcription box protein P3 (FOXP3). Environmental factors, such as vitamin D deficiency, Zn, Se, and Mg, as well as infections, chronic stress, pregnancy, smoking, alcohol, medications, intestinal dysbiosis, and malnutrition, also play an important role. The first stage of autoimmunization involves the accumulation of macrophages and dendritic cells, as well as plasma cells. In the second stage, the mutual interactions of individual cells in the immune system lead to a decrease in the level of CD8+ in favor of CD4+, which intensifies the synthesis of T lymphocyte derivatives, especially Th1, Th17, Tfh, and Tc, reducing the level of Treg. Consequently, the number of the anti-inflammatory cytokines IL10 and IL2 decreases, and the synthesis of the pro-inflammatory cytokines IL-2, Il-12, Il-17, IL-21, IL-22, IFN-γ, and TNF-α increases. The latter two especially trigger the pyroptosis process involving the inflammasome. Activation of the inflammasome by IL-β and IL-18 produced by macrophages is one of the mechanisms of pyroptosis in the course of Hashimoto\'s thyroiditis, involving Gram-negative bacteria and NLRC4. In the next step, the apoptosis of thyroid cells is initiated by the intensification of perforin, granzyme, and proteoglycan synthesis by Tc and NK cells. The current findings raise many possibilities regarding interventions related to the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines produced by both T and B lymphocytes. Furthermore, since there is currently no effective method for treating thyroid autoimmunity, a summary of the review may provide answers regarding the treatment of not only Hashimoto\'s thyroiditis, but also other autoimmune diseases associated with autoimmunity.
摘要：
甲状腺自身免疫的过程是在与II类人类白细胞抗原（HLA-DR）相关的遗传易感性的背景下发展的，以及细胞毒性T淋巴细胞相关蛋白4（CTLA-4），蛋白酪氨酸磷酸酶非受体22型（PTPN22），和叉头转录盒蛋白P3(FOXP3)。环境因素,如维生素D缺乏，Zn,Se,Mg,以及感染，慢性压力，怀孕,吸烟,酒精,药物,肠道生态失调，营养不良，也起着重要的作用。自身免疫的第一阶段涉及巨噬细胞和树突状细胞的积累，以及浆细胞。在第二阶段,免疫系统中单个细胞的相互作用导致CD8+水平降低，而CD4+，增强了T淋巴细胞衍生物的合成，尤其是Th1,Th17,Tfh,还有Tc,降低Treg水平。因此,抗炎细胞因子IL10和IL2的数量减少，和促炎细胞因子IL-2，IL-12，IL-17，IL-21，IL-22，IFN-γ的合成，和TNF-α增加。后两者特别触发涉及炎性体的焦亡过程。巨噬细胞产生的IL-β和IL-18对炎症小体的激活是桥本甲状腺炎过程中焦亡的机制之一，涉及革兰氏阴性菌和NLRC4。下一步,甲状腺细胞的凋亡是由穿孔素的增强引发的，granzyme,Tc和NK细胞合成蛋白聚糖。当前的发现提出了关于与抑制促炎细胞因子和刺激由T和B淋巴细胞产生的抗炎细胞因子相关的干预措施的许多可能性。此外，由于目前尚无治疗甲状腺自身免疫的有效方法,这篇综述的摘要不仅可以提供关于桥本甲状腺炎治疗的答案，还有其他与自身免疫相关的自身免疫性疾病。
