The biology and therapeutic potential of interleukin 27

Batten, Marcel; Ghilardi, Nico

doi:10.1007/s00109-007-0164-7

Cited by 109 publications

(136 citation statements)

References 83 publications

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“…IL-6/IL-12 family cytokines, namely, IL-12, IL-23, and IL-27, are mainly produced by APC such as DC and macrophages in response to infection with intracellular pathogens [1][2][3]. These cytokines play important roles in bridging innate and adaptive immunities [1][2][3] and are structurally and functionally related.…”

Section: Introductionmentioning

confidence: 99%

“…These cytokines play important roles in bridging innate and adaptive immunities [1][2][3] and are structurally and functionally related. IL-12 and IL-23 proteins share a common p40 subunit, but contain unique p35 and p19 subunits, respectively [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…IL-12 and IL-23 proteins share a common p40 subunit, but contain unique p35 and p19 subunits, respectively [1,2]. IL-27 is composed of EBV-induced gene 3 and p28 that are homologous to p40 and p35 subunits, respectively [1,3]. The functional receptors for IL-12 and IL-23 share IL-12Rb1 but contain unique IL-12Rb2 and IL-23R, respectively [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…The functional receptors for IL-12 and IL-23 share IL-12Rb1 but contain unique IL-12Rb2 and IL-23R, respectively [1,2]. The IL-27 receptor complex is composed of WSX-1 and gp130; the former confers ligand specificity and the latter is shared by other IL-6 family cytokines [1,3]. IL-12 acts on naive or memory T cells and promotes the differentiation into IFN-c-producing Th1 cells.…”

Section: Introductionmentioning

confidence: 99%

“…IL-23 is thus essential for the development of inflammatory autoimmune diseases as well as antimicrobial defense [5,6]. The function of IL-27 is rather complex; it acts on naive T cells and primes Th1 development in synergy with IL-12; however, at later phases of infection, IL-27 suppresses IFN-c and IL-17A production in Th1 and Th17 cells, respectively [1,3].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

Kanda¹,

Watanabe²

2008

Eur J Immunol

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IL-12, IL-23, and IL-27, which are produced by APC, modulate innate and adaptive immunities. Human b-defensin-2 (hBD-2) produced by epidermal keratinocytes promotes cutaneous antimicrobial defense and inflammation. We examined the in vitro effects of IL-12, IL-23, and IL-27 on hBD-2 production in human keratinocytes. IL-12, IL-23, and IL-27 enhanced IL-1b-induced hBD-2 secretion and mRNA expression in keratinocytes. The stimulatory effects of IL-12, IL-23, and IL-27 were suppressed by antisense oligonucleotides against NF-jB p50 and p65. In addition, the effects of IL-12 and IL-27 were suppressed by antisense STAT3 and STAT1, respectively. All the three IL enhanced the basal and IL-1b-induced transcriptional activities of NF-jB, while IL-12 and IL-27 enhanced STAT3 and STAT1 activities, respectively. Further, IL-12, IL-23, and IL-27 promoted basal and IL-1b-induced phosphorylation of IjBa. IL-12 and IL-23 tyrosine phosphorylated STAT3 and STAT1, respectively; IL-12, IL-23, and IL-27 tyrosine phosphorylated JAK2 and tyrosine kinase-2; and IL-27 tyrosine phosphorylated JAK1. These results suggest that IL-12, IL-23, and IL-27 may enhance IL-1b-induced hBD-2 production in keratinocytes by activating NF-jB. STAT3 and STAT1 are involved in the effects of IL-12 and IL-27, respectively. Thus, IL-12, IL-23, and IL-27 may promote cutaneous antimicrobial defense and inflammation via hBD-2.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

Kanda¹,

Watanabe²

2008

Eur J Immunol

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Th17 Cells

Noack

Miossec

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Interleukin‐27 inhibits human osteoclastogenesis by abrogating RANKL‐mediated induction of nuclear factor of activated T cells c1 and suppressing proximal RANK signaling

Kalliolias¹,

Zhao²,

Triantafyllopoulou³

et al. 2010

Arthritis & Rheumatism

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Objective. Interleukin-27 (IL-27) has stimulatory and regulatory immune functions and is expressed in rheumatoid arthritis (RA) synovium. This study was undertaken to investigate the effects of IL-27 on human osteoclastogenesis, to determine whether IL-27 can stimulate or attenuate the osteoclast-mediated bone resorption that is a hallmark of RA.Methods. Osteoclasts were generated from bloodderived human CD14؉ cells. The effects of IL-27 on osteoclast formation were evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells and measuring the expression of osteoclast-related genes. The induction of nuclear factor of activated T cells c1 (NFATc1) and the activation of signaling pathways downstream of RANK were measured by immunoblotting. The expression of key molecules implicated in osteoclastogenesis (NFATc1, RANK, costimulatory receptors, and immunoreceptor tyrosinebased activation motif-harboring adaptor proteins) was measured by real-time reverse transcriptionpolymerase chain reaction. Murine osteoclast precursors obtained from mouse bone marrow and synovial fluid macrophages derived from RA patients were also tested for their responsiveness to IL-27.Results. IL-27 inhibited human osteoclastogenesis, suppressed the induction of NFATc1, downregulated the expression of RANK and triggering receptor expressed on myeloid cells 2 (TREM-2), and inhibited RANKL-mediated activation of ERK, p38, and NF-B in osteoclast precursors. Synovial fluid macrophages from RA patients were refractory to the effects of IL-27. In contrast to the findings in humans, IL-27 only moderately suppressed murine osteoclastogenesis, and this was likely attributable to low expression of the IL-27 receptor subunit WSX-1 on murine osteoclast precursors.Conclusion. IL-27 inhibits human osteoclastogenesis by a direct mechanism that suppresses the responses of osteoclast precursors to RANKL. These findings suggest that, in addition to its well-known antiinflammatory effects, IL-27 plays a homeostatic role in restraining bone erosion. This homeostatic function is compromised under conditions of chronic inflammation such as in RA synovitis.Interleukin-27 (IL-27) is a member of the IL-12 family of heterodimeric cytokines that also includes . IL-27 comprises the Epstein-Barr virus-induced protein 3 and p28 subunits, which share similarity with the p40 and p35 subunits of IL-12, respectively (4). The IL-27 receptor is a heterodimer composed of a WSX-1 subunit (also termed T cell cytokine receptor), which confers ligand specificity, and the gp130 signaling subunit, which is also utilized by the IL-6 family of cytokines (5). IL-27 activates the JAK/STAT signal transduction pathway in a contextdependent manner, since its effects vary depending on Dr.

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The biology and therapeutic potential of interleukin 27

Cited by 109 publications

References 83 publications

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

Th17 Cells

Interleukin‐27 inhibits human osteoclastogenesis by abrogating RANKL‐mediated induction of nuclear factor of activated T cells c1 and suppressing proximal RANK signaling

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