Laboratorio de Genética y Microevolución, Facultad de Ciencias Básicas, Universidad Católica del Maule, Talca 3466706, Chile.
Doctorado en Modelamiento Matemático Aplicado, Facultad de Ciencias Básicas, Universidad Católica del Maule, Talca 3466706, Chile.
Endocrinology. 2021 Dec 1;162(12). doi: 10.1210/endocr/bqab190.
Hashimoto thyroiditis (HT) is a pathology that often causes a gradual thyroid insufficiency in affected patients due to the autoimmune destruction of this gland. The cellular immune response mediated by T helper lymphocytes TH1 and TH17 can induce the HT disease. In this pathologic condition, there is an imbalance between the TH17 and Treg lymphocytes as well as a gut microbiota dysfunction. The objective of this work was to describe the interactions of the cell subpopulations that participate in HT. To achieve this goal, we generated a mathematical model that allowed the simulation of different scenarios for the dynamic interaction between thyroid cells, the immune system, and the gut microbiota. We used a hypothetical-deductive design of mathematical modeling based on a system of ordinary differential equations, where the state variables are the TH1, TH17, and Treg lymphocytes, the thyrocytes, and the bacteria from gut microbiota. This work generated a compartmental model of the cellular immune response occurring in the thyroid gland. It was observed that TH1 and TH17 lymphocytes could increase the immune cells' activity, as well as activate effector cells directly and trigger the apoptosis and inflammation processes of healthy thyrocytes indirectly. Likewise, the model showed that a reduction in Treg lymphocytes could increase the activity of TH17 lymphocytes when an imbalance of the gut microbiota composition occurred. The numerical results highlight the TH1, TH17, and bacterial balance of the gut microbiota activities as important factors for the development of HT disease.
桥本甲状腺炎（HT）是一种病理学，由于该腺体的自身免疫破坏，常导致受影响患者逐渐出现甲状腺功能不全。辅助性 T 淋巴细胞 TH1 和 TH17 介导的细胞免疫反应可诱发 HT 疾病。在这种病理状态下，TH17 和 Treg 淋巴细胞之间存在不平衡以及肠道微生物群功能障碍。本工作旨在描述参与 HT 的细胞亚群之间的相互作用。为了实现这一目标，我们生成了一个数学模型，该模型允许模拟甲状腺细胞、免疫系统和肠道微生物群之间动态相互作用的不同情况。我们使用了基于常微分方程系统的数学建模的假设演绎设计，其中状态变量是 TH1、TH17 和 Treg 淋巴细胞、甲状腺细胞和来自肠道微生物群的细菌。这项工作生成了发生在甲状腺中的细胞免疫反应的分区模型。观察到 TH1 和 TH17 淋巴细胞可以增加免疫细胞的活性，以及直接激活效应细胞，并间接触发健康甲状腺细胞的凋亡和炎症过程。同样，该模型表明，当肠道微生物群组成失衡时，Treg 淋巴细胞的减少会增加 TH17 淋巴细胞的活性。数值结果强调了肠道微生物群活动的 TH1、TH17 和细菌平衡是 HT 疾病发展的重要因素。
