Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd,, Houston, TX 77030, USA.
Cell Commun Signal. 2013 Dec 13;11:95. doi: 10.1186/1478-811X-11-95.
Studies into the regulation of interleukin-10 (IL-10), have focused only on the molecular or single-cell level. The cues that induce IL-10 in the context of cell-to-cell communication are scarce. To fill this gap, this study elucidates the cell-to-cell interaction dependent regulation of IL-10.
The simultaneous activation of CD4+ T cells via CD3/CD28 and stimulation of macrophages via CpG and their intercellular communication with each other in the same microenvironment is necessary to induce a synergistic expression of IL-10. NF-κB1, ERK, and STAT3 are positive regulators of this cell-to-cell communication mediated molecular change of IL-10 induction. Strikingly, the activation of CD40/CD154 signaling is a negative regulator of IL-10 levels by CD3/CD28/CpG.
These findings are of prominence as CD3/CD28/CpG treatment can induce the anti-inflammatory cytokines IL-10 and IL-30, and the activation or inhibition of the CD40/CD154 acts as molecular rheostat of the expression of IL-10 or IL-30. More importantly, this not only serves as an example of IL-10 regulation at the cellular via coordination of two signals from two cell types, but these findings also lay the molecular and cellular groundwork for future studies to investigate how to manipulate IL-10 or IL-30 production during inflammation, cancer, or autoimmune diseases.
白细胞介素-10（IL-10）的调节研究仅集中在分子或单细胞水平。诱导细胞间通讯中 IL-10 的线索很少。为了填补这一空白，本研究阐明了依赖于细胞间相互作用的 IL-10 调节。
在相同的微环境中，通过 CD3/CD28 同时激活 CD4+T 细胞，并通过 CpG 刺激巨噬细胞，并使它们相互间进行细胞间通讯，是诱导 IL-10 协同表达所必需的。NF-κB1、ERK 和 STAT3 是这种细胞间通讯介导的 IL-10 诱导分子变化的正调节剂。引人注目的是，CD40/CD154 信号的激活是 CD3/CD28/CpG 诱导的 IL-10 水平的负调节剂。
这些发现意义重大，因为 CD3/CD28/CpG 处理可以诱导抗炎细胞因子 IL-10 和 IL-30，而 CD40/CD154 的激活或抑制可作为 IL-10 或 IL-30 表达的分子变阻器。更重要的是，这不仅为通过两种细胞类型的两种信号的协调来调节细胞中的 IL-10 提供了一个范例，而且这些发现还为未来研究如何在炎症、癌症或自身免疫性疾病期间操纵 IL-10 或 IL-30 的产生奠定了分子和细胞基础。
