The cytokine network type I IFN-IL-27-IL-10 is augmented in murine and human lupus.

IL-10 is elevated in the autoimmune disease systemic lupus erythematosus (SLE). Here, we show that conventional dendritic cells (cDCs) from predisease lupus-prone B6.NZM Sle1/Sle2/Sle3 triple congenic (TCSle) mice produce more IL-10 than wild-type congenic cDCs upon TLR stimulation, and this overproduction is prevented by blocking the type I IFN receptor (IFNAR) with specific Abs.

Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf.

Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1.

Prostaglandin E2 Inhibition of IL-27 Production in Murine Dendritic Cells: A Novel Mechanism That Involves IRF1.

IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function.

The natural dual cyclooxygenase and 5-lipoxygenase inhibitor flavocoxid is protective in EAE through effects on Th1/Th17 differentiation and macrophage/microglia activation.

Prostaglandins and leukotrienes, bioactive mediators generated by cyclooxygenases (COX) and 5-lipoxygenase (5-LO) from arachidonic acid, play an essential role in neuroinflammation. High levels of LTB4 and PGE2 and increased expression of COX and 5-LO, as well as high expression of PGE2 receptors were reported in multiple sclerosis (MS) patients and in experimental autoimmune encephalomyelitis (EAE). Prostaglandins and leukotrienes have an interdependent and compensatory role in EAE, which led to the concept of therapy using dual COX/5-LO inhibitors.

Differential effects of IFN-β on IL-12, IL-23, and IL-10 expression in TLR-stimulated dendritic cells.

MS is an autoimmune disease characterized by immune cell infiltration in the CNS, leading to cumulative disability. IFN-β, used clinically in RR-MS reduces lesion formation and rates of relapse. Although the molecular mechanisms are not entirely elucidated, myeloid cells appear to be a major target for the therapeutic effects of IFN-β.

Enhancement of glioma-specific immunity in mice by "NOBEL", an insulin-like growth factor 1 receptor antisense oligodeoxynucleotide.

Autologous glioblastoma multiforme tumor cells treated with an antisense oligodeoxynucleotide (AS-ODN) targeting insulin-like growth factor receptor-1 (IGF-1R) are the basis of a vaccine with therapeutic effects on tumor recurrence in a pilot clinical trial. As a preface to continued clinical investigation of this vaccination strategy, we have studied the contribution of an optimized IGF-1R AS-ODN, designated "NOBEL", to the induction of immunity to mouse GL261 glioma cells. The impact of NOBEL on mechanisms contributing to the development of GL261 immunity was first examined in the periphery.

Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm.

Glioblastomas are primary intracranial tumors for which there is no cure. Patients receiving standard of care, chemotherapy and irradiation, survive approximately 15 months prompting studies of alternative therapies including vaccination. In a pilot study, a vaccine consisting of Lucite diffusion chambers containing irradiated autologous tumor cells pre-treated with an antisense oligodeoxynucleotide (AS-ODN) directed against the insulin-like growth factor type 1 receptor was found to elicit positive clinical responses in 8/12 patients when implanted in the rectus sheath for 24 h.

IL-1R1 signaling facilitates Munro's microabscess formation in psoriasiform imiquimod-induced skin inflammation.

Munro's microabscesses contain polymorphonuclear leukocytes and form specifically in the epidermis of psoriasis patients. The mechanism whereby the neutrophils are recruited into the epidermis is poorly understood. Using a combination of human and mouse primary keratinocyte cell cultures and the imiquimod-induced psoriasis-like mouse model of skin inflammation, we explored the role of IL-1 signaling in microabscess formation.