TY - JOUR
T1 - Coordination between TLR9 signaling in macrophages and CD3 signaling in T cells induces robust expression of IL-30
AU - Dibra, Denada
AU - Cutrera, Jeffry J.
AU - Li, Shulin
PY - 2012/4/15
Y1 - 2012/4/15
N2 - IL-30, the p28 subunit of IL-27, interacts with EBV-induced gene 3 to form IL-27, which modulates both proinflammatory and antiinflammatory 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 invitro mirrors the murine model in which administration of CpG under inflammatory conditions invivo 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.
AB - IL-30, the p28 subunit of IL-27, interacts with EBV-induced gene 3 to form IL-27, which modulates both proinflammatory and antiinflammatory 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 invitro mirrors the murine model in which administration of CpG under inflammatory conditions invivo 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.
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U2 - 10.4049/jimmunol.1100883
DO - 10.4049/jimmunol.1100883
M3 - Article
C2 - 22407920
AN - SCOPUS:84860338292
SN - 0022-1767
VL - 188
SP - 3709
EP - 3715
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -