INTERLEUKIN 10 RECEPTOR COMPLEX

描述(改编自《调查者摘要》)：细胞因子 白介素10(IL-10)对免疫有广泛的影响 系统从抑制到刺激各种功能和细胞。 鉴定并克隆了一条与IL-10结合的受体链(IL-10R1)， 然而，这种单一受体链的存在并不能解释 IL-10的所有作用。因此，我们开始确定第二个 IL-10受体复合体的链并能够定义和 初步鉴定第二个链，命名为IL-10R2。鉴于 每条链本身不能赋予细胞对IL-10的全部反应性， 这两条链的组合可以。具有身份标识的 第二链，IL-10R2，关于功能性的一些问题 现在可以接近IL-10受体复合体了。这份提案是专门设计的 回答有关IL-10R2链在介质中的作用的问题 IL-10在免疫系统和某些癌症中的作用。整体而言 这一提议背后的假设是，两个受体链都是 IL-10的功能所必需的。结果将使我们能够理解 IL-10如何在免疫系统中发挥作用。另外，由于爱泼斯坦- 巴尔病毒(EBV)产生一种IL-10的病毒同源物，命名为VIL-10， 我们将研究IL-10和VIL-10之间的活性差异 这应该有助于深入了解VIL-10在EBV相关疾病中的作用 恶性肿瘤。这项研究的具体目的是：1)胡士泰的作用-- IL-10功能中的IL-10R2链；2)确定IL-10如何抑制 其他细胞因子的功能；3)IL-10R2基因的调节；4) 测定IL-10的mRNAs和IL-10受体链的调节 (IL-10R1和IL-10R2)；5)定义细胞功能的差异 和病毒IL-10。我们的结果应该确立第二种观点的作用 链在IL-10受体中的作用，加深了我们对IL-10是如何 功能，并提供了对EBV蛋白VIL-10的作用的洞察 在EB病毒诱导的癌症中。此外，由于IL-10是一种重要的 免疫抑制细胞因子在免疫功能中的作用 T细胞亚群，所获得的知识应该有助于我们理解 IL-10介导免疫抑制的机制。

DESCRIPTION (Adapted from Investigator's Abstract): The cytokine interleukin-10 (IL-10) exhibits a wide spectrum of effects on the immune system from inhibition to stimulation of various functions and cells. One receptor chain that binds IL-10 was identified and cloned (IL-10R1), however, the existence of this single receptor chain could not explain all the effects of IL-10. Accordingly, we set out to identify the second chain of the IL-10 receptor complex and were able to define and initially characterize the second chain, designated IL-10R2. Whereas each chain alone cannot impart full responsiveness of cells to IL-10, the combination of both chains can. With the identification of the second chain, IL-10R2, a number of questions regarding the functional IL-10 receptor complex can now be approached. This proposal is designed to answer questions about the role of the IL-10R2 chain in mediating IL-10 effects in the immune system and in some cancers. The overall hypothesis underlying this proposal is that both receptor chains are required for function of IL-10. The results will enable us to understand how IL-10 functions in the immune system. In addition, since Epstein- Barr virus (EBV) produces a viral homolog of IL-10 designated vIL-10, we will examine the differences in activity between IL-10 and vIL-10 that should provide insight into the role of vIL-10 in EBV-related malignancies. Specific aims of this study are: 1) the role of the Hu- IL-10R2 chain in IL-10 function; 2) determine how IL-10 inhibits functions of other cytokines; 3) regulation of the IL-10R2 gene; 4) determine regulation of the mRNAs of IL-10 and the IL-10 receptor chains (IL-10R1 and IL-10R2); 5) define the differences in function of cellular and viral IL-10. Our results should establish the role of the second chain in IL-10 receptor function, enhance our understanding of how IL-10 functions, and provide insight into the role of the EBV protein vIL-10 in EBV-induced cancers. Furthermore, because IL-10 is an important immunosuppressive cytokine in immune function such as in development of T-cell subsets, the knowledge gained should help us understand the mechanisms by which IL-10 mediates immunosuppression.