Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation
Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation
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DOI：
10.4049/jimmunol.167.12.6884
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发表时间：
2001-12-15
影响因子：
4.4
通讯作者：
Bromberg, JS
中科院分区：
文献类型：
--
作者：
Ding, YZ;Qin, LH;Bromberg, JS
在这项研究中，我们的特点是不同的受体结合特异性，亲和力，和Janus激酶STAT激活细胞IL-10（cIL-10）相比，病毒IL-10（vIL-10）。只有表达IL-10 R1的细胞才能结合人IL-10或vIL-10。IL-10 R2不单独与cIL-10或vIL-10结合，并且其存在不增强cIL-10或vIL-10的受体结合亲和力，但其对于cIL-10和vIL-10介导的信号转导和免疫调节都是必需的。在B细胞和肥大细胞系中比较了cIL-10和vIL-10引发的应答，并证明与人IL-10相比，vIL-10不能刺激免疫应答是由于不能引发信号传导。缺乏信号转导是由于细胞表面IL-10 R1的低水平表达，因为过表达IL-10 R1允许vIL-10启动cIL-10样信号和随后的生物学应答。这些结果在原代细胞中是相似的，因为脾细胞对cIL-10和vIL-10都有应答，而胸腺细胞仅对cIL-10有应答，并且具有非常低的小鼠IL-10 R1表达，但没有小鼠IL-10 R2表达。这些数据表明，IL-10 R1表达在确定细胞是否响应IL-10中起关键作用。细胞表面IL-10 R1密度的调节可能是确定IL-10是否导致体内免疫刺激或免疫抑制的重要机制。
In this study, we characterized the differential receptor-binding specificity, affinity, and Janus kinase-STAT activation of cellular IL-10 (cIL-10) compared with viral IL-10 (vIL-10). Only cells expressing IL-10R1 bind human IL-10 or vIL-10. IL-10R2 does not bind to cIL-10 or vIL-10 alone and its presence does not enhance the receptor-binding affinity of cIL-10 or vIL-10, but it is essential for both cIL-10- and vIL-10-mediated signal transduction and immune regulation. Responses initiated by cIL-10 and vIL-10 were compared in B cell and mast cell lines, and demonstrated that the inability of vIL-10 to stimulate immune responses, as compared with human IL-10, is due to failure to initiate signaling. Absent signal transduction is due to low level expression of cell surface IL-10R1, since overexpressing IL-10R1 allows vIL-10 to initiate cIL-10-like signals and subsequent biological responses. These results are similar in primary cells, since splenocytes respond to both cIL-10 and vIL-10, while thymocytes respond only to cIL-10 and have very low mouse IL-10R1 but not mouse IL-10R2 expression. These data demonstrate that IL-10R1 expression plays a critical role in determining whether cells respond to IL-10. Modulation of cell surface IL-10R1 density might be an important mechanism for determining whether IL-10 leads to immunostimulation or immunosuppression in vivo.