Disease relevance of IL27

• Although signaling of IL-27/WSX-1 interactions have been recognized in the down-regulation of airway hyper-reactivity and in lung inflammation during the development of allergic asthma, little is known about the role of single nucleotide polymorphisms (SNPs) of IL-27 and individual susceptibility to asthma [1].
• In contrast, in all lymphomas tested, no or few tumoral cells expressed p28 [2].
• Interleukin (IL)-27 is a novel heterodimeric cytokine of the IL-12 family that is composed of two subunits, Epstein-Barr virus (EBV)-induced gene 3 (EBI3) and p28 [2].
• B16F10 + IL-27 cells exerted antitumor activity against not only s.c. tumor but also experimental pulmonary metastasis [3].
• In this study, we further evaluated the antitumor and antiangiogenic activities of IL-27, using poorly immunogenic murine melanoma B16F10 tumors, which were engineered to overexpress single-chain IL-27 (B16F10 + IL-27) [3].

High impact information on IL27

• IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells [4].
• Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system [5].
• Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells [6].
• We found that LPS-stimulated p28 production was completely dependent on the Toll-like receptor 4/myeloid differentiation factor 88 (MyD88)-mediated pathway but only partially dependent on nuclear factor kappaB c-Rel [7].
• Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-{gamma}-mediated pathways [7].

Biological context of IL27

• We show that neither of the two subunits itself is sufficient to mediate IL-27-induced signal transduction, but that the combination of both is required for this event [8].
• We report here that IL-27 induces Stat1 and Stat3 phosphorylation and activation in human and murine cell lines and primary human T cells [9].
• Differential expression of proteins within the p28/p30-Omp locus may therefore be vital for adaptation of Ehrlichia species to their dual host life cycle [10].

Anatomical context of IL27

• IL-27 is a novel heterodimeric cytokine of the IL-12 family that plays an important role in the regulation of T cell responses [11].
• Differential Effects of IL-27 on Human B Cell Subsets [11].
• Consistent with these data, no significant p28 or IL-27 expression was detected in HL-derived cell lines, or in EBV- or HTLV-1-transformed cell lines [2].
• Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4(+) T cells, it also directly acts on cells of the innate immune system [8].
• Moreover, B16F10 + IL-27 cells clearly inhibited angiogenesis by dorsal air sac method, and IL-27 exhibited dose-dependent inhibition of angiogenesis on chick embryo chorioallantoic membrane [3].

Associations of IL27 with chemical compounds

• WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27 [8].
• The recent identification of a progestin membrane receptor and the sub cellular targeted nuclear receptor isoforms ER46, mtRXR, mtPPAR, p28 and p46, has highlighted the potential importance of non-genomic actions of steroid hormones [12].

Regulatory relationships of IL27

• Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27 [13].
• Interleukin-27 (IL-27) supports proliferation of naive CD4(+) T cells and enhances interferon-gamma (IFN-gamma) production by activated T cells and natural killer (NK) cells [9].
• IL-27 also suppressed IL-17 production by activated CD4(+) T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects [13].
• IL-27 activated a STAT1-dominant pattern of signaling in human monocytes with the consequent activation of STAT1-dependent inflammatory target genes [14].

Other interactions of IL27

• In addition, IL-27 increased proliferation of anti-Ig-activated naive B cells and of anti-CD40-activated naive and germinal center B cells, but not of CD40-activated memory B cells [11].
• The IL-27 cytokine is mediated by one of the receptor chains (WSX-1) of the IL-27 receptor that is highly expressed on CD4(+) T lymphocytes and NK cells [1].
• These data indicate that the B cell response to IL-27 is modulated during B cell differentiation and varies depending on the mode of B cell activation [11].
• In this study, we investigated EBI3 and p28 expression in normal human B lymphocytes and in non-EBV-associated B-cell lymphomas [15].
• Though elucidation of the Jak/STAT signaling pathways activated by IL-27R ligation has unveiled some of the molecular mechanisms used by IL-27 to promote inflammation, little is known about the anti-inflammatory activities of this cytokine [16].

References