The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity

Aparicio-Siegmund, Samadhi; Garbers, Christoph

doi:10.1016/j.cytogfr.2015.07.008

Cited by 71 publications

(61 citation statements)

References 98 publications

(141 reference statements)

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“…Interleukin-27 is a cytokine with known immunomodulatory properties involved in the pathogenesis of numerous diseases (5, 6). Several types of infections also course with an increase of IL-27 (23–25).…”

Section: Discussionmentioning

confidence: 99%

“…Interleukin-27 is mainly produced by macrophages and dendritic cells (DCs) after the stimulation of surface receptors such as TLRs or CD40 and following IFNs signaling (5, 6). Although this cytokine was initially described as pro-inflammatory, numerous anti-inflammatory and immunomodulatory properties are recognized today [reviewed in Ref.…”

Section: Introductionmentioning

confidence: 99%

“…Although this cytokine was initially described as pro-inflammatory, numerous anti-inflammatory and immunomodulatory properties are recognized today [reviewed in Ref. (5, 6)].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

et al. 2016

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The complexity of Leishmania–host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two classical susceptible visceral leishmaniasis mouse models. BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after infection, which was associated with an upregulation of IL-27p28 expression by dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely infected BALB/c led to decreased parasite burdens and a transient increase in IFN-γ+ splenic T cells, while administration of IL-27 to C57BL/6 promoted a local anti-inflammatory cytokine response at the site of infection and increased parasite loads. Overall, we show that, as in humans, BALB/c IL-27 systemic levels are infection dependently upregulated and may favor parasite installation by controlling inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

et al. 2016

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“…15 Ligation of the IL-27 receptor induces signaling through the Jak/STAT pathway, resulting in the phosphorylation of STAT1, 3, 5, or 6. 7,16 In addition to the Jak/STAT pathway, the activated IL-27 receptor has been reported to induce p38MAPK, ERK, and Akt signaling. IL-27 signaling also induces SOCS3, a suppressor of IL-27 signaling that directly binds to and inhibits the gp130 receptor subunit and associated Janus kinases and later facilitates their degradation.…”

Section: Il-27 and Its Receptormentioning

confidence: 99%

“…IL-27 signaling also induces SOCS3, a suppressor of IL-27 signaling that directly binds to and inhibits the gp130 receptor subunit and associated Janus kinases and later facilitates their degradation. 7 …”

Section: Il-27 and Its Receptormentioning

confidence: 99%

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

Andrews

McLean

Durum

2016

Inflammatory Bowel Diseases

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Inflammatory bowel disease (IBD) is an inflammatory disorder of the intestine that affects an estimated 329 per 100,000 people in the United States and is increasing in incidence within a number of cultures worldwide. Likely due to its incompletely understood pathophysiology and etiology, standard treatments for IBD are only efficacious in subsets of patients and often do not induce lasting remission. As a result, novel therapies are needed. The success of anti-tumor necrosis factor-α treatment in a subset of IBD patients demonstrated that therapy targeting a single cytokine could be efficacious in IBD, and clinical trials investigating the blockade of a variety of cytokines have commenced. IL-27 is a relatively recently discovered type I cytokine with established roles in infectious disease, autoimmunity, and cancer in a variety of organs. IL-27 was identified as a candidate gene for IBD, and a number of studies in mouse models of IBD have demonstrated that IL-27 therapy is protective. However, in contrast to these investigations, genetic deletion of the IL-27 receptor has been shown to be protective in some mouse models of IBD. The purpose of this review is to highlight recent literature investigating the role of IL-27 in IBD, and to discuss possible explanations for the sometimes conflicting results of these studies. Evidence supporting IL-27 therapy as a treatment for IBD will also be discussed.

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Glycosaminoglycans bind human IL‐27 and regulate its activity

et al. 2020

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IL-27 is a cytokine of the IL-12 family, composed of EBI3 and IL-27p28. IL-27 regulates immune responses and also other physiological processes including hematopoiesis, angiogenesis, and bone formation. Its receptor, composed of IL-27Rα and gp130, activates the STAT pathway. Here, we show that different glycosaminoglycans (GAGs) modulate human IL-27 activity in vitro. We find that soluble heparin and heparan sulfate efficiently inhibit human IL-27 activity as shown by decreased STAT signaling and downstream biological effects. In contrast, membrane-bound heparan sulfate seems to positively regulate IL-27 activity. Our biochemical studies demonstrate that soluble GAGs directly bind to human IL-27, consistent with in silico analyses, and prevent its binding to IL-27Rα. Although murine IL-27 also bound to GAGs in vitro, its activity was less efficiently inhibited by soluble GAGs. Lastly, we show that two heparin-derivatives, low molecular weight heparin and fondaparinux, that like unfractionated heparin are used in clinics, had weaker or no effect on human IL-27 activity. Together, our data identify GAGs as new players in the regulation of human IL-27 activity that might act under physiological conditions and may also have a clinical impact in heparin-treated patients.

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The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity

Cited by 71 publications

References 98 publications

Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

Glycosaminoglycans bind human IL‐27 and regulate its activity

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