The control of allergic conjunctivitis by suppressor of cytokine signaling (SOCS)3 and SOCS5 in a murine model
The control of allergic conjunctivitis by suppressor of cytokine signaling (SOCS)3 and SOCS5 in a murine model
复制标题
DOI：
10.4049/jimmunol.175.8.5489
复制
发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Kubo, M
中科院分区：
文献类型：
--
作者：
Ozaki, A;Seki, Y;Kubo, M
过敏性结膜炎(AC)是一种常见的过敏性眼病，以瘙痒、结膜充血、Ag特异性IgE升高、肥大细胞活化和局部嗜酸性粒细胞浸润为特征。在本研究中，我们建立了一种Ag诱导的AC小鼠模型，以了解该病的发病机制。细胞转移实验表明，AC可分为早相反应和晚期反应(EPR和LPR)。EPR与IgE反应相关，导致瘙痒，而LPR以局部嗜酸性粒细胞浸润为特征。在STAT6基因缺陷的小鼠中，EPR和LPR均受到显著抑制，过继转移Th2细胞重建了LPR。此外，SOCS3在发病部位高表达，并且SOCS3的T细胞特异性表达恶化了AC的临床和病理特征，表明Th2介导的SOCS3的表达控制了AC的发生和持续。SOCS3杂合子小鼠的表达水平降低或显性阴性SOCS3转基因小鼠的功能抑制明显降低了AC的严重程度。相反，SOCS5，一种IL-4信号的特异性抑制剂，结构性表达，导致嗜酸性粒细胞浸润减少。这些结果表明，显性-负性SOCS3和SOCS5对Th2介导的反应的负性调节可能是变态反应性疾病治疗干预的靶点。
Allergic conjunctivitis (AC) is a common allergic eye disease characterized by clinical symptoms such as itchiness, conjunctival congestion, elevated Ag-specific IgE, mast cell activation, and local eosinophil infiltration. In this study we established a murine model for Ag-induced AC to understand the pathogenesis of the disease. Cell transfer experiments indicated that AC can be divided into early and late phase responses (EPR and LPR). EPR was associated with IgE responses, leading to itchiness, whereas LPR was characterized by local eosinophil infiltration. Both EPR and LPR were significantly inhibited in STAT6-deficient mice, and adoptive transfer of Th2 cells reconstituted LPR. Furthermore, SOCS3 was highly expressed at the disease site, and T cell-specific expression of SOCS3 deteriorated clinical and pathological features of AC, indicating that Th2-mediated SOCS3 expression controls the development and persistence of AC. Reduction of the expression level in SOCS3 heterozygous mice or inhibition of function in dominant-negative SOCS3 transgenic mice clearly reduced the severity of AC. In contrast, constitutive expression of SOCS5, a specific inhibitor of IL-4 signaling, resulted in reduced eosinophil infiltration. These results suggest that negative regulation of the Th2-mediated response by dominant-negative SOCS3 and SOCS5 could be a target for therapeutic intervention in allergic disease.