Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: Induction of the B cell-activating chemokine, CXC chemokine ligand 13
Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: Induction of the B cell-activating chemokine, CXC chemokine ligand 13
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DOI：
10.4049/jimmunol.172.11.7031
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Mantovani, A
中科院分区：
文献类型：
--
作者：
Perrier, P;Martinez, FO;Mantovani, A
为了了解IL-10对树突状细胞（DC）功能的调节，利用Affymetrix技术（Santa Clara， CA）对IL-10单独或与LPS联合处理的人单核细胞来源DC进行了基因表达谱分析。所选基因的调节通过实时PCR、Northern blot和蛋白生产验证。IL-10在DC中调控有限数量基因的表达，包括IL-7、转铁蛋白和维生素D-3受体、结构基质蛋白和信号转导元件。与LPS单独处理相比，LPS加IL-10联合处理可调节许多基因，但表达谱不同。正如预期的那样，IL-10抑制了几种lps诱导的促炎分子的表达。在LPS + IL-10联合治疗的独特调节基因中，磷脂酰肌醇3-激酶γ下调，细胞因子信号传导抑制因子3、淋巴细胞活化信号传导分子、G蛋白信号传导调节因子16和趋化因子CXC趋化因子配体（CXCL） 13上调。总的来说，确定了四个不同的转录程序，它们与：1)免疫和炎症的控制；2)细胞因子受体和G蛋白偶联受体信号的调控；3)细胞外基质重塑；B细胞功能与淋巴组织新生。在后一种基因中，我们进一步证明IL-10与TLR配体协同作用，在髓细胞和浆细胞样DC中产生功能活跃的B细胞吸引趋化因子CXCL13。这一新发现表明，IL-10通过诱导apc中趋化因子CXCL13的产生来维持免疫，CXCL13可扩增B细胞募集并促进淋巴组织新生。
To understand the modulation of dendritic cell (DC) function by IL-10, gene expression profiling was performed by using Affymetrix technology (Santa Clara, CA) in human monocyte-derived DC treated with IL-10, alone or in combination with LPS. The modulation of selected genes was validated by real-time PCR, Northern blot, and protein production. IL-10 regulated in DC the expression of a limited number of genes, including IL-7, the receptors for transferrin and vitamin D-3, structural matrix proteins, and signal transduction elements. The combined treatment with LPS plus IL-10 modulated a number of genes comparable to LPS alone, but the expression profiles were distinct. As expected, IL-10 suppressed the expression of several LPS-inducible proinflammatory molecules. Among genes uniquely modulated by the concomitant treatment with LPS plus IL-10, phosphatidylinositol 3-kinase gamma was down-regulated while the suppressor of cytokine signaling 3, signaling lymphocytic activation molecule, regulator of G protein signaling 16, and the chemokine, CXC chemokine ligand (CXCL) 13, were up-regulated. Overall, four distinct transcriptional programs were identified, related to: 1) control of immunity and inflammation; 2) tuning of cytokine receptor and G protein-coupled receptor signaling; 3) remodeling of extracellular matrix; and 4) B cell function and lymphoid tissue neogenesis. Among the latter genes, we further demonstrate that IL-10 synergizes with TLR ligands for the production of functionally active B cell-attracting chemokine, CXCL13, in both myeloid and plasmacytoid DC. This novel finding reveals that IL-10 sustains Immoral immunity by inducing the production in APCs of the chemokine, CXCL13, which amplifies B cell recruitment and promotes lymphoid tissue neogenesis.