Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM et al.Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7:937-945

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6008, USA.
Nature Immunology (Impact Factor: 20). 10/2006; 7(9):937-45. DOI: 10.1038/ni1376
Source: PubMed


Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T(H)-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.

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Available from: Alejandro V Villarino, Feb 02, 2015
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    • "Similar to IL-12, IL-27 is also able to prompt IFN-gamma production from naive CD4+ T cells5 IL-27 promotes the T helper cell (Th1) differentiation through up-regulating T-box expressed in T cells (T-bet)7 and Intercellular Adhesion Molecule 1 (ICAM-1).6 However, it inhibits the differentiation toward Th2,8,9 Th17 type responses10,11 and the production of pro-inflammatory cytokines.12,13 IL-27 together with the transforming growth factor beta (TGF-β) plays a critical role in generating IL-10-producing anti-inflammatory Type 1 regulatory T (Tr1) cells.14 "
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    ABSTRACT: Background: Interleukin (IL)-23 and IL-27 are two IL-12-related cytokines which their function may dramatically influence the inflammatory response to tumor development. IL-12 and IL-27 seem to have antagonistic roles with IL-23 in tumor site. In this study, IL-23 and IL-27 mRNA expressions were analyzed in peripheral blood of patients with breast cancer and healthy volunteers using quantitative real-time PCR. Methods: Peripheral blood samples were collected from 50 women with breast cancer and 50 healthy ones. The total RNA was extracted from peripheral blood after lysis with ammonium chloride and TRizol reagent and the cDNA was synthesized. The expression of IL-23 and IL-27 gene transcripts was determined with real-time polymerase chain reaction (qRT-PCR) using Syber Green PCR Master Mix. Results: It is found that IL-23 and IL-27 transcripts had significantly higher expression in peripheral blood of patients compared with the healthy controls. The ratio of IL-23 transcript expression to IL-27 was 3.4 fold lower in the studied patients compared with the normal individuals. Conclusion: It is concluded that the over expression of IL-23 and IL-27 gene transcript in peripheral blood of breast cancer patients may be an immune response against tumor development and the inflammatory response plays a critical role in tumor development via up regulating the corresponding cytokines. However, the IL-23/IL-27 ratio may play an important role in cytokine-based immunotherapy against cancer. Further research should be carried out to assess these cytokines in a larger sample size. .
    Iranian Journal of Medical Sciences 07/2014; 39(4):350-6.
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    • "IL-27 signals through the common gp130 subunit and the IL-27-specific WSX-1 subunit, which is upregulated upon T cell activation [90, 91]. IL-27 suppresses the development of Th17 cells in a STAT1-dependent manner [92, 93] and suppresses IL-6-mediated T cell proliferation, not surprisingly as IL-6 and IL-27 both signal through the shared receptor component gp130 [89, 92]. IL-27 has been shown capable of suppressing the ability of diseased lymph node and spleen cells to confer EAE on healthy mice and was able to suppress autoreactive Th17 cells in vitro and in vivo [94]. "
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    ABSTRACT: Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.
    Clinical and Developmental Immunology 12/2013; 2013(7):986789. DOI:10.1155/2013/986789 · 2.93 Impact Factor
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    • "In support of these theories, CD4+ T cells from WSX-1−/− mice are hyper proliferative following in vitro stimulation with anti-CD3/CD28 [6], [10] and proliferate more extensively in the lungs of WSX-1−/− mice than WT mice during Mycobacterium tuberculosis infection [9]. Whilst the role of IL-27 in controlling T cell apoptosis has not been directly examined, IL-6 and IL-12 are both known to exert anti-apoptotic effects on CD4+ T cells [11], [12] and concentrations of both these cytokines are significantly increased in WSX-1−/− mice during infection [9], [10], [13], [14]. Alternatively, IL-27 might limit the autonomous chemotactic activity of CD4+ T cells, and/or affect the expression of liver derived chemotactic/migratory factors. "
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    ABSTRACT: IL-27 is an important and non-redundant regulator of effector T cell accumulation in non-lymphoid tissues during infection. Using malaria as a model systemic pro-inflammatory infection, we demonstrate that the aberrant accumulation of CD4(+) T cells in the liver of infected IL27R(-/-) (WSX-1(-/-)) mice is a result of differences in cellular recruitment, rather than changes in T cell proliferation or cell death. We show that IL-27 both inhibits the migratory capacity of infection-derived CD4(+) T cells towards infection-derived liver cells, but also suppresses the production of soluble liver-derived mediator(s) that direct CD4(+) T cell movement towards the inflamed tissue. Although CCL4 and CCL5 expression was higher in livers of infected WSX-1(-/-) mice than infected WT mice, and hepatic CD4(+) T cells from WSX-1(-/-) mice expressed higher levels of CCR5 than cells from WT mice, migration of CD4(+) T cells to the liver of WSX-1(-/-) mice during infection was not controlled by chemokine (R) signalling. However, anti-IL-12p40 treatment reduced migration of CD4(+) T cells towards infection-derived liver cells, primarily by abrogating the hepatotropic migratory capacity of T cells, rather than diminishing soluble tissue-derived migratory signals. These results indicate that IL-27R signalling restricts CD4(+) T cell accumulation within the liver during infection primarily by suppressing T cell chemotaxis, which may be linked to its capacity to repress Th1 differentiation, as well as by inhibiting the production of soluble, tissue-derived chemotaxins.
    PLoS ONE 11/2013; 8(11):e78486. DOI:10.1371/journal.pone.0078486 · 3.23 Impact Factor
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