IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice

Fujimoto, Hirokazu; Hirase, Tetsuaki; Miyazaki, Y.; Hara, Hiromitsu; Ide-Iwata, Noriko; Nishimoto-Hazuku, Ai; Saris, Christiaan J. M.; Yoshida, Hiroki; Node, Koichi

doi:10.1016/j.ajpath.2011.08.001

Cited by 35 publications

(24 citation statements)

References 35 publications

(39 reference statements)

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“…Immunoregulation by immunosuppressive cytokines in local lesions of arterial walls is considered to be beneficial to prevent atherosclerosis and related diseases. We also reported in C57BL/6 mice that IL-27 inhibits pancreatic ␤ cell injury by macrophage-mediated islet inflammation that contributes to the development of diabetes (5). Accordingly, we suggest that anti-inflammatory IL-27-IL-27 receptor could be a favorable therapeutic target for vascular and metabolic diseases whereby chronic inflammation driven at least partly by macrophages plays important roles.…”

Section: Ldlr-/-wsx-1-/-mentioning

confidence: 74%

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice

Hirase

Hara

Miyazaki

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic inflammation in arterial wall that is driven by immune cells and cytokines plays pivotal roles in the development of atherosclerosis. Interleukin 27 (IL-27) is a member of the IL-12 family of cytokines that consists of IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3) and has anti-inflammatory properties that regulate T cell polarization and cytokine production. IL-27-deficient (Ldlr-/-Ebi3-/-) and IL-27 receptor-deficient (Ldlr-/-WSX-1-/-) Ldlr-/- mice were generated and fed with a high-cholesterol diet to induce atherosclerosis. Roles of bone marrow-derived cells in vivo and macrophages in vitro were studied using bone marrow reconstitution by transplantation and cultured peritoneal macrophages, respectively. We demonstrate that mice lacking IL-27 or IL-27 receptor are more susceptible to atherosclerosis compared with wild type due to enhanced accumulation and activation of macrophages in arterial walls. The number of circulating proinflammatory Ly6C(hi) monocytes showed no significant difference between wild-type mice and mice lacking IL-27 or IL-27 receptor. Administration of IL-27 suppressed the development of atherosclerosis in vivo and macrophage activation in vitro that was indicated by increased uptake of modified low-density lipoprotein and augmented production of proinflammatory cytokines. These findings define a novel inhibitory role for IL-27 in atherosclerosis that regulates macrophage activation in mice.

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Section: Ldlr-/-wsx-1-/-mentioning

confidence: 74%

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice

Hirase

Hara

Miyazaki

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Additionally, the abilities of IL-27 to promote the expression of PD-1 and PD-L1 and to activate Treg cells indicate that IL-27 acts as a regulatory hub that coordinates multiple regulatory pathways; thus, this may strengthen the rationale for targeting this cytokine therapeutically. Models of infectious and autoimmune systems continue to identify new effects of IL-27, but IL-27 is implicated in disease outcome in other areas-such as metabolic diseases (226,227) and diabetes (228,229)-that are relatively unexplored. Regardless, there is still a need to better understand the context-dependent functions of what IL-27 does to T cells to promote regulatory activities versus inflammatory functions, and there remains a need for data sets that utilize genomic approaches to further our understanding of the impact of IL-27 on different immune populations.…”

Section: Discussionmentioning

confidence: 98%

The Immunobiology of Interleukin-27

Yoshida

Hunter

2015

Annu. Rev. Immunol.

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361

433

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Interleukin-27 (IL-27) is a cytokine with strikingly diverse influences on the immune response. Although it was initially linked with the development of Th1 responses, it is now recognized as a potent antagonist of different classes of inflammation through its ability to directly modify CD4(+) and CD8(+) T cell effector functions, to induce IL-10, and to promote specialized T regulatory cell responses. Although this aspect of IL-27 biology has provided insights into how the immune system prevents hyperactivity in the setting of infectious and autoimmune inflammation, in vaccination and cancer models the stimulatory effects of IL-27 on CD8(+) T cell function appear prominent. Additionally, associations between IL-27 and antibody-mediated disease have led to an interest in defining the impact of IL-27 on innate immunity and humoral responses in different disease states. The maturation of this literature has been accompanied by attempts to translate these findings from experimental models into human diseases and by efforts to define where IL-27 might represent a viable therapeutic target.

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“…Mice deficient in IL-27 subunit (EBI3−/−) or IL-27 receptor subunit (WSX-1−/−) mice) treated with STZ for induction of diabetes showed increased blood glucose and islet proinsulin levels as well as enhanced immune cell infiltration into the islets compared to wild type controls [124]. Furthermore, treatment of EBI3−/− and wild type mice with IL-27 led to reduction of these disease-associated parameters, demonstrating the immunoregulatory role of IL-27 in this model of T1D [124].…”

Section: Involvement Of Il-27 In the Pathogenesis Of Autoimmune DImentioning

confidence: 99%

“…Furthermore, treatment of EBI3−/− and wild type mice with IL-27 led to reduction of these disease-associated parameters, demonstrating the immunoregulatory role of IL-27 in this model of T1D [124]. …”

Section: Involvement Of Il-27 In the Pathogenesis Of Autoimmune DImentioning

confidence: 99%

IL-27-induced modulation of autoimmunity and its therapeutic potential

Meka

Venkatesha

Dudics

et al. 2015

Autoimmunity Reviews

147

130

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Interleukin-27 (IL-27) is a new member of the IL-12 family. It is produced by activated antigen-presenting cells and plays an important role in the regulation of CD4+ T cell differentiation and immune response. IL-27 activates multiple signaling cascades, including the JAK-STAT and p38 MAPK pathways. Several studies have revealed that IL-27 promotes the differentiation of Th1 and Tr1, but inhibits Th2, Th17, and Treg cells. However, a few studies have shown an opposite effect on certain T cell subsets, such as Treg. IL-27 displays both pro- and anti- inflammatory activities in different autoimmune diseases. Here, we have discussed the role of IL-27 in rheumatoid arthritis, multiple sclerosis, colitis, lupus, psoriasis, type 1 diabetes, and uveitis. Most of this information is derived from experimental models of these autoimmune diseases. The mechanistic basis of the dual role of IL-27 in inflammation and autoimmunity is still not fully defined. In general, the pro-/ anti- inflammatory activity of IL-27 is influenced by the underlying immune effector pathways, the phase of the disease, the presence or absence of counter-regulatory cytokines/T cell subsets, and the tissue/cell type under study. Despite a spectrum of outcomes in various autoimmune diseases, mostly anti-inflammatory and immunomodulatory effects of IL-27 have been observed in this category of diseases. Accordingly, IL-27 represents a novel, promising target/agent for the treatment of autoimmune diseases.

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IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice

Cited by 35 publications

References 35 publications

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice

The Immunobiology of Interleukin-27

IL-27-induced modulation of autoimmunity and its therapeutic potential

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