Gianoukakis Andrew G, Khadavi Nicole, Smith Terry J
Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Thyroid. 2008 Sep;18(9):953-8. doi: 10.1089/thy.2007.0405.
Graves' disease, an autoimmune process associated with thyroid dysfunction, can also manifest as remodeling of orbital connective tissue. Affected tissues exhibit immune responses that appear to be orchestrated by resident cells and those recruited from the bone marrow through their expression and release of cytokines and surface display of cytokine receptors. Cytokines are small molecules produced by many types of cells, including those of the "professional" immune system. Aberrant cytokine expression appears to play an important role in the pathogenesis of many human diseases, including thyroid autoimmunity. The skewed pattern of cytokine expression in the thyroid, including the T helper cell bias, may condition the response to apoptotic signals and determine the characteristics of an autoimmune reaction. Furthermore, chemoattractant cytokines, including IL16, RANTES, and CXCL10, elaborated by resident cells in the thyroid and orbit may provoke mononuclear cell infiltration. Other cytokines may drive cell activation and tissue remodeling. Thus cytokines and the signaling pathways they activate represent attractive therapeutic targets. Interruption of these might alter the natural course of Graves' disease and its orbital manifestations.
格雷夫斯病是一种与甲状腺功能障碍相关的自身免疫过程,也可表现为眼眶结缔组织重塑。受影响的组织表现出免疫反应,这些反应似乎是由驻留细胞以及通过细胞因子的表达和释放以及细胞因子受体的表面展示从骨髓募集来的细胞所协调的。细胞因子是由多种类型的细胞产生的小分子,包括“专业”免疫系统的细胞。异常的细胞因子表达似乎在许多人类疾病的发病机制中起重要作用,包括甲状腺自身免疫。甲状腺中细胞因子表达的偏态模式,包括辅助性T细胞偏差,可能会影响对凋亡信号的反应并决定自身免疫反应的特征。此外,甲状腺和眼眶中的驻留细胞产生的趋化因子细胞因子,包括白细胞介素16、调节激活正常T细胞表达和分泌的趋化因子(RANTES)和CXC趋化因子10,可能会引发单核细胞浸润。其他细胞因子可能驱动细胞活化和组织重塑。因此,细胞因子及其激活的信号通路是有吸引力的治疗靶点。阻断这些可能会改变格雷夫斯病及其眼眶表现的自然病程。