Advances in understanding the anti-inflammatory properties of IL-27

Abstract

Initial studies on the biology of IL-27 provided evidence of a role for this cytokine in the initiation of Th1 responses; however, subsequent work using models of pathogen-induced and autoimmune inflammation have indicated that IL-27 has broad inhibitory effects on Th1, Th2 and Th17 subsets of T cells as well as the expansion of inducible regulatory T cells. While, the aim of this review is to highlight the functions of IL-27 in the context of inflammation it will also serve to elaborate on the molecular mechanisms involved in the production of this cytokine. The initial description of IL-27 indicated that classical antigen-presenting cells such as macrophages and dendritic cells produce IL-27, however, the agonists and signaling pathways involved in activating transcription of the two subunits of IL-27, p28 and EBV-induced gene 3 (EBI3) have only recently been described.

Fig. 1

Transcriptional Regulation of IL-27p28 and EBI3. Expression of IL-27 p28 and EBI3 are upregulated through a MyD88 or TRIF dependent signaling cascade in antigen presenting cells following stimulation with the TLR4 agonist LPS. Additionally, type I and II interferons can induce p28 transcription in an IRF1 dependent manner.

Fig. 2

IL-27 induces CD4⁺ T cells to produce IL-10. The release of IL-10 by T cells subsequently serves as a broad inhibitor of accessory cell function by downregulating expression of MHC and co-stimulatory molecules, and inhibiting the release of pro-inflammatory cytokines; thus, diminishing T cell activation and an ongoing inflammatory response.