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

• Published in: The Journal of immunology (1950) 2004-06, Vol.172 (11), p.7031-7042
• Main Authors: Perrier, Patrick, Martinez, Fernando O, Locati, Massimo, Bianchi, Giancarlo, Nebuloni, Manuela, Vago, Gianluca, Bazzoni, Flavia, Sozzani, Silvano, Allavena, Paola, Mantovani, Alberto
• Format: Article
• Language: English
• Subjects: Chemokine CXCL13; Chemokines, CXC - biosynthesis; Dendritic Cells - metabolism; Eye Proteins - physiology; Gene Expression Profiling; Humans; Interleukin-10 - pharmacology; Lipopolysaccharides - pharmacology; Oligonucleotide Array Sequence Analysis; Receptors, Chemokine; Receptors, CXCR5; Receptors, Cytokine - physiology; Repressor Proteins - physiology; RGS Proteins - physiology; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transcription Factors - physiology; Transcriptional Activation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.11.7031

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 humoral immunity by inducing the production in APCs of the chemokine, CXCL13, which amplifies B cell recruitment and promotes lymphoid tissue neogenesis.