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The molecule IL-27 is critical in limiting the immune response to the parasite Toxoplasma gondii . In the absence of IL-27, a lethal, overactive immune response develops during infection. However, when exactly in the course of infection this molecule is needed was unclear. By selectively inhibiting IL-27 during this parasitic infection, we discovered that IL-27 was only needed during, but not prior to, infection. Additionally, IL-27 is only needed in the active areas in which the parasite is replicating. Finally, our work found that a previously unstudied cell type, monocytes, was regulated by IL-27, which contributes further to our understanding of the regulatory networks established by this molecule.

Interleukin (IL)-27, a member of IL-12/IL-23 heterodimeric family of cytokines, has pleiotropic properties that can enhance or limit immune responses. IL-27 acts on various cell types, including T cells, B cells, macrophages, dendritic cells, natural killer (NK) cells and non-hematopoietic cells. Intensive studies have been conducted especially on T cells, revealing that various subsets of T cells respond uniquely to IL-27. IL-27 induces expansion of Th1 cells by activating signal transducer and activator of transcription (STAT) 1-mediated T-bet signaling pathway. On the other hand, IL-27 suppresses immune responses through inhibition of the development of T helper (Th) 17 cells and induction of IL-10 production in a STAT1- and STAT3-dependent manner. IL-27 is a potentially promising cytokine for therapeutic approaches on various human diseases. Here, we provide an overview of the biology of IL-27 related to T cell subsets, its structure, and production mechanism.

The newly generated CD4 single-positive (SP) T lymphocytes are featured by enhanced IL-4 but repressed IFN-γ production. The mechanisms underlying this functional bias remain elusive. Previous studies have reported that CD4 + T cells from mice harboring dendritic cell (DC)-specific deletion of IL-27p28 display an increased capacity of IFN-γ production upon TCR stimulation. Here, we demonstrated that similarly altered functionality occurred in CD4SP thymocytes, recent thymic emigrants (RTEs), as well as naive T cells from either Cd11c-p28 f/f mice or mice deficient in the α subunit of IL-27 receptor. Therefore, DC-derived IL-27p28-triggered, IL-27Rα-mediated signal is critically involved in the establishment of functional bias against IFN-γ production during their development in the thymus. Epigenetic analyses indicated reduced DNA methylation of the Ifng locus and increased trimethylation of H3K4 at both Ifng and Tbx21 loci in CD4SP thymocytes from Cd11c-p28 f/f mice. Transcriptome profiling demonstrated that Il27p28 ablation resulted in the coordinated up-regulation of STAT1-activated genes. Concurrently, STAT1 was found to be constitutively activated. Moreover, we observed increased accumulation of STAT1 at the Ifng and Tbx21 loci and a strong correlation between STAT1 binding and H3K4me3 modification of these loci. Of note, Il27p28 deficiency exacerbated the autoimmune phenotype of Aire -/- mice. Collectively, this study reveals a novel mechanism underlying the functional bias of newly generated CD4 + T cells and the potential relevance of such a bias in autoimmunity.

Background and objectivesInterleukin 27 (IL-27) is a cytokine consisting of two subunits, p28 and EBI3, and is a key mediator in regulating the differentiation of TCD4 + cells while playing a crucial role in immune-related disorders. This study aims to elucidate the possible association between IL-27p28 single nucleotide polymorphisms (SNPs), IL-27 serum levels, and the risk of allergic rhinitis (AR).Materials and methodsBlood samples were collected from 130 patients with AR and 130 healthy individuals, and DNA and serum were separated. The relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR was evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. The serum levels of IL-27 in the participants were determined using enzyme-linked immunosorbent assay.ResultsOur results did not show a significant relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR or serum IL-27 levels. However, our results showed a significant decrease in the serum level of IL-27 in patients with AR (342 ± 299 pg/mL) compared to healthy subjects (455 ± 274 pg/mL) (p = 0.02).ConclusionOur results suggest that IL-27p28 SNPs (rs181206 and rs153109) are not associated with susceptibility to AR, but that decreased serum IL-27 levels may be associated with the development of AR.