IL-27 p28/IL-30 Signaling Pathways

Click on the other IL-6 family cytokines listed below to see the signaling pathways that are activated by each cytokine. Refer to the table below each pathway to see a select list of cytokine-expressing cells or tissues and the primary biological effects induced by the different members of the IL-6 cytokine family.

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IL-27 p28/IL-30
IL-27 p28/IL-30
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CLF
CLF
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IL-27 p28/
IL-30
IL-27 p28/
IL-30
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CLF
CLF
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IL-27 p28/IL-30
Secretion
IL-27 p28/IL-30
Secretion
sIL-6 R alpha
sIL-6 R alpha
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IL-27 p28/IL-30
IL-27 p28/IL-30
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CLF
CLF
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CLF
CLF
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gp130
gp130
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IL-27 p28/IL-30
IL-27 p28/IL-30
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sIL-6 R alpha
sIL-6 R alpha
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Trans Signaling
Trans Signaling
IL-27 p28/IL-30
Signaling
IL-27 p28/IL-30
Signaling
High Concentration
IL-27 p28/IL-30
High Concentration
IL-27 p28/IL-30
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IL-27 p28/IL-30
IL-27 p28/IL-30
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gp130
gp130
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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IL-27 p28/IL-30
Signaling
IL-27 p28/IL-30
Signaling
Classic Signaling
Classic Signaling
CLF
CLF
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gp130
gp130
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IL-27 R alpha
IL-27 R alpha
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IL-27 p28/IL-30
IL-27 p28/IL-30
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IL-6 R alpha
IL-6 R alpha
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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OR
OR
IL-6 R alpha
IL-6 R alpha
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IL-27 p28/IL-30
IL-27 p28/IL-30
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CLF
CLF
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CLF
CLF
IL-6 R
alpha
IL-6 R
alpha
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IL-27 p28/IL-30
IL-27 p28/IL-30
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gp130
gp130
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IL-27 p28/IL-30
IL-27 p28/IL-30
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CLF
CLF
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IL-6 R alpha
IL-6 R alpha
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IL-27 p28/IL-30
IL-27 p28/IL-30
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CLF
CLF
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CLF
CLF
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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STAT1
STAT1
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STAT3
STAT3
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STAT5
STAT5
STAT Dimer
STAT Dimer
STAT Dimer
STAT Dimer

Overview of IL-27 p28/IL-30 Signaling Pathways

IL-27 p28/IL-30 is a member of the IL-6 cytokine family, which also includes IL-6, IL-11, IL-31, Leukemia inhibitory factor (LIF), Oncostatin M (OSM), Cardiotrophin-like cytokine (CLC), Ciliary neurotrophic factor (CNTF), Cardiotrophin-1 (CT-1), and Neuropoietin. IL-27 p28, also known as IL-30, is a four-helix bundle cytokine that associates with Epstein-Barr virus-induced gene 3 (EBI3) to form the heterodimeric IL-27 cytokine. In addition to its pairing with EBI3, IL-27 p28/IL-30 can also associate with Cytokine-like factor-1 (CLF-1), to form a complex that is secreted by dendritic cells. While CLF-1 is required for IL-27 p28/IL-30 secretion, it is not required for receptor recognition or downstream signaling. IL-27 p28/IL-30 has been reported to signal through either a tripartite receptor complex consisting of IL-6 R alpha, IL-27 R alpha/WSX-1, and gp130 or a multi-subunit receptor complex consisting of IL-6 R alpha coupled with a gp130 homodimer. Like IL-6, IL-27 p28/IL-30 is thought to be capable of initiating both classic and trans-signaling by binding to either the membrane-bound or soluble forms of IL-6 R alpha, respectively. Both the classic and trans-signaling ligand-receptor complexes induce STAT3 and STAT1 phosphorylation in target cells, and presumably, promote the activation of additional intracellular signaling pathways as well, although this hasn’t been directly shown. While the biological significance of the classic and trans-signaling pathways has yet to be clarified, the finding that IL-27 p28/IL-30 can activate both pathways suggests that IL-27 p28/IL-30 could have a wide range of effects on multiple different cell types. Additionally, IL-27 p28/IL-30 is reportedly capable of signaling through gp130 alone when present at high concentrations due to its high affinity for gp130. The biological effects associated with IL-27 p28/IL-30 to date include up-regulation of natural killer cell activation and IL-2- or IL-12-induced IFN-gamma production, inhibition of anti-CD3-, anti-CD28-induced CD4+ T cell proliferation, induction of T cell production of IL-10, promotion of Th17 differentiation in the presence of TGF-beta and inhibition of IL-6/ TGF-beta-induced Th17 differentiation, stimulation of plasma cell differentiation, and protection against cytokine-induced liver injury.

To learn more, please visit our IL-6 Family Research Area page.

Primary IL-27 p28/IL-30-Expressing Cells Primary Biological Effects of the IL-27 p28/IL-30:CLF-1 Composite Cytokine
Dendritic cells Up-regulates natural killer cell activation and IFN-gamma production in the presence of IL-2 or IL-12
Macrophages Induces IL-10 secretion by CD4+ T cells and inhibits anti-CD3/CD28-induced proliferation
  Promotes Th17 differentiation in the presence of TGF-beta in vitro and can inhibit IL-6-, TGF-beta-induced Th17 differentiation
  Induces the differentiation of B cells into antibody-secreting plasma cells
  Protects against cytokine-induced liver injury

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