IL-27 expression regulation and its effects on adaptive immunity against viruses

Abstract

IL-27, a member of the IL-6/IL-12 cytokine superfamily, is primarily secreted by antigen presenting cells, specifically by dendric cells, macrophages and B cells. IL-27 has antiviral activities and modulates both innate and adaptive immune responses against viruses. The role of IL-27 in the setting of viral infections is not well defined and both pro-inflammatory and anti-inflammatory functions have been described. Here, we discuss the latest advancements in the role of IL-27 in several viral infection models of human disease. We highlight important aspects of IL-27 expression regulation, the critical cell sources at different stages of the infection and their impact in cell mediated immunity. Lastly, we discuss the need to better define the antiviral and modulatory (pro-inflammatory vs anti-inflammatory) properties of IL-27 in the context of human chronic viral infections.

Keywords: CD8 T cells; IL-27 (interleukin 27); IL-27 viral immunity; IL-27 viral infection; IL-27/IL-27R.

Figure 1

The IL-12 family of cytokines. The IL-12 family of cytokines are heterodimers that result from the combination of one of three alpha (α) chains (p19, p28 or p35), with one of two beta (β) chains (p40 or EBI3). The association of the α and β chains results in heterodimers that share a common element among the family members. The receptors of this family of cytokines are heterodimeric molecules shared by the family members. The cytokines of this family signal through the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (JAK/STAT) pathway (Figure was designed with BioRender.com).

Figure 2

IL-27 cell sources and cellular responses during viral infection. IL-27 has antiviral activities that are prominent early after infection. IL-27 is mainly produced by antigen presenting cells (APCs) including dendritic cells (DCs), plasma cells, macrophages, monocytes, microglia, B cells and endothelial cells. IL-27 plays critical role by modulating adaptive cellular responses against viruses. The beneficial effects include reducing immunopathology and viral control, in contrast in some infections showed a predominant regulatory function leading to viral persistence. (Figure was created with BioRender.com).