Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Cell Transplant. 2023 Jan-Dec;32:9636897231204075. doi: 10.1177/09636897231204075.
Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves' disease (GD) and high levels of thyroid hormones (THs) can drive the progression of GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.
B 细胞耐受的破坏和异常激活是格雷夫斯病（GD）发病机制中的一个重要机制，而甲状腺激素（THs）水平升高可驱动 GD 的进展。然而，THs 与 GD 背景下 B 细胞异常激活之间的相互作用尚不清楚。本研究旨在探讨 B 细胞激活因子（BAFF）介导 THs 和 B 细胞之间的串扰及其潜在机制。使用高水平三碘甲状腺原氨酸（T3）小鼠模型来验证 T3 介导的 BAFF 过表达和 B 细胞异常分化的诱导。还研究了 T3 极化到 M1 时是否可能促进小鼠脾脏巨噬细胞中 BAFF 的过表达。结果表明，高水平的 T3 可诱导 BAFF 过表达并导致小鼠 B 细胞异常分化。虽然在小鼠的许多组织类型中均观察到 BAFF 的过表达，但高水平的 T3 可通过 IFN（干扰素-γ）-γ在小鼠脾脏中诱导 M1 巨噬细胞极化，从而产生 BAFF 过表达。本研究结果为内分泌和免疫系统之间的相互作用提供了新的见解，并深入了解了 TH 在 GD 发病机制中的作用。
