IL-27-Induced Gene Expression Is Downregulated in HIV-Infected Subjects

Abstract

ObjectiveTo characterize the effect of HIV infection on IL-27-induced gene expression.DesignDuring HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR.ResultsExpression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects.ConclusionIn HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.

IL-27 Promotes Human Placenta–Derived Mesenchymal Stromal Cell Ability To Induce the Generation of CD4+IL-10+IFN-γ+ T Cells via the JAK/STAT Pathway in the Treatment of Experimental Graft-versus-Host Disease

“…FCM was used with PBMC as positive control (35). The results demonstrated that both gp130 and IL-27Ra were expressed in hPMSCs (Fig.…”

Evaluating the potential of IL-27 as a novel therapeutic agent in HIV-1 infection

“…Some studies have also looked at whether cells obtained directly from HIV-1 infected donors have an impaired response to IL-27. Exogenous IL-27 was administered to monocytes from HIV-1 infected donors and their responsiveness was compared to monocytes from uninfected controls [41]. In monocytes obtained from HIV-1 infected donors, IL-27 treatment led to lower levels of expression of the IL-27 receptor subunit, gp130, compared to healthy controls.…”

Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4

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