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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.

Original publication

DOI

10.4049/jimmunol.172.11.7031

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

06/2004

Volume

172

Pages

7031 - 7042

Addresses

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Keywords

Dendritic Cells, Humans, Lipopolysaccharides, RGS Proteins, Eye Proteins, Receptors, Chemokine, Receptors, Cytokine, Transcription Factors, Repressor Proteins, Chemokines, CXC, Interleukin-10, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Suppressor of Cytokine Signaling Proteins, Receptors, CXCR5, Chemokine CXCL13, Transcriptional Activation, Suppressor of Cytokine Signaling 3 Protein