Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
J Immunol. 2010 Jan 15;184(2):550-4. doi: 10.4049/jimmunol.0903152. Epub 2009 Dec 11.
Proinflammatory Th1 cells can produce large amounts of the immunosuppressive cytokine IL-10, thereby facilitating the self-limitation of inflammatory responses. Recently, we identified the Notch pathway as a main regulator of IL-10 production by Th1 cells. In this study, we show that plasmacytoid dendritic cells (pDCs), by means of their unique high-level expression of the Notch ligand Delta-like (Dll)-4, activate the Notch receptor on T cells to induce robust IL-10 production in vitro and in vivo. pDCs display a distinct pattern of Notch ligands compared with conventional dendritic cells, marked by the constitutive expression of Dll-4, the only Notch ligand to induce IL-10 expression in vivo, and Dll-1, while at the same time lacking the expression of Jagged. We provide a new mechanism for IL-10 induction by pDCs underlining the importance of the Dll-4/Notch axis in the regulation of inflammatory T cell responses.
促炎性 Th1 细胞能够产生大量免疫抑制细胞因子 IL-10，从而促进炎症反应的自我限制。最近，我们发现 Notch 途径是 Th1 细胞产生 IL-10 的主要调节因子。在这项研究中，我们表明浆细胞样树突状细胞（pDCs）通过其独特的高水平表达 Notch 配体 Delta-like（Dll）-4，激活 T 细胞上的 Notch 受体，从而在体外和体内诱导强烈的 IL-10 产生。pDCs 与传统树突状细胞相比具有明显不同的 Notch 配体模式，其特征是组成性表达 Dll-4，这是唯一一种能够在体内诱导 IL-10 表达的 Notch 配体，同时缺乏 Jagged 的表达。我们为 pDCs 诱导 IL-10 提供了一个新的机制，强调了 Dll-4/Notch 轴在调节炎症性 T 细胞反应中的重要性。
