title: Coordination between TLR9 signaling in macrophages and CD3 signaling in T cells induces robust expression of IL-30.
abstract: 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.
authors.affiliation: Department of Pediatrics Research, Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Denada
authors.initials: D
authors.lastname: Dibra
authors.forename: Jeffry J
authors.initials: JJ
authors.lastname: Cutrera
authors.forename: Shulin
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D005786:Gene Expression Regulation; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D018106:CD28 Antigens; D017252:CD3 Complex; C486767:Il27 protein, mouse; D007378:Interleukins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9