Coordination between TLR9 signaling in macrophages and CD3 signaling in T cells induces robust expression of IL-30

• Published in: The Journal of immunology (1950) Vol. 188; no. 8; pp. 3709 - 3715
• Main Authors: Dibra, Denada, Cutrera, Jeffry J, Li, Shulin
• Format: Journal Article
• Language: English
• Published: United States 15-04-2012
• Subjects: Animals; Antibodies, Neutralizing; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD28 Antigens - immunology; CD3 Complex - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Communication; Gene Expression Regulation; Interleukins - genetics; Interleukins - immunology; Interleukins - metabolism; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Knockout; Myeloid Differentiation Factor 88 - deficiency; Myeloid Differentiation Factor 88 - immunology; Oligodeoxyribonucleotides - pharmacology; Signal Transduction; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1100883

IL-30, the p28 subunit of IL-27, interacts with EBV-induced gene 3 to form IL-27, which modulates both proinflammatory and anti-inflammatory responses during autoimmune or infectious disease. It also acts as a natural antagonist of gp130, thereby attenuating the signals of other gp130-associated cytokines. IL-30 regulation via LPS has been reported by others, but the intercellular communication that induces IL-30 expression is unknown. In this study, we show that treatment with anti-CD3/CD28 Abs plus CpG oligodeoxynucleotides induces robust expression of IL-30, whereas either treatment alone induces only low expression of IL-30. This observation in vitro mirrors the murine model in which administration of CpG under inflammatory conditions in vivo induces IL-30 expression. This robust induction of IL-30 occurs through the coordination of helper CD4(+) T cells and innate immune cells (e.g., macrophages) and, to a lesser degree, B cells via the CD40/CD154 signaling pathway. These findings reveal a previously unrecognized mechanism that integrates signaling pathways from T cells and macrophages at the cellular level to induce IL-30 expression.