Type III Interferon Signaling Pathways

Click on one of the buttons below to see the signaling pathways that are activated by members of either the type I or type II interferon families.

Type III IFN
Type III IFN
IL-10 R beta/
IL-10 R2
IL-10 R beta/
IL-10 R2
IL-28 R alpha/IFN-lambda R1
IL-28 R alpha/IFN-lambda R1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Vav
Vav
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GEFs
GEFs
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Rac1
Rac1
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MAPKKK
MAPKKK
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MKK3
MKK3
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MKK6
MKK6
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p38
p38
MNK1/2
MNK1/2
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MAPKAPK2/3
MAPKAPK2/3
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MSK1/2
MSK1/2
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CREB
CREB
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Histone H3
Histone H3
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Growth
Inhibition

Growth
Inhibition

Chromatin Remodeling
Chromatin Remodeling
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STAT1
STAT2
STAT1
STAT2
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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ISGF3
ISGF3
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STAT1
STAT1
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STAT2
STAT2
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IRF9
IRF9
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IFN-Stimulated Genes
IFN-Stimulated Genes
Anti-Viral Response
Anti-Viral Response
STAT1
STAT3
STAT4
STAT5
STAT1
STAT3
STAT4
STAT5
Homo-/
Heterodimers
Homo-/
Heterodimers
STAT Dimer
STAT Dimer
Regulation of the
Inflammatory Response
Regulation of the
Inflammatory Response

ISRE

ISRE

GAS

GAS

Overview of Type III Interferon Signaling Pathways

The type III interferon family consists of four proteins, IL-29/IFN-lambda 1, IL-28A/IFN-lambda 2, IL-28B/IFN-lambda 3, and IFN-lambda 4, which are distantly related to members of the IL-10 and type I IFN cytokine families. IL-29/IFN-lambda 1 is found only in humans and is 81% homologous to IL-28A/IFN-lambda 2 and IL-28B/IFN-lambda 3, which share 96% amino acid identity. IFN-lambda 4 was originally thought to be a pseudogene but it’s since been found that a dinucleotide frameshift variant can generate a functional IFN-lambda 4 protein. All type III IFNs bind to a receptor complex formed by the IL-28 R alpha/IFN-lambda R1 ligand-binding subunit and the IL-10 R beta accessory chain. Like type I IFNs, type III IFNs activate Jak1 and Tyk2, leading to the phosphorylation and activation of STAT1 and STAT2. Phosphorylated STAT1 and STAT2 associate with IRF9 to form the ISGF3 complex, which subsequently translocates to the nucleus and regulates the expression of ISGs. In addition, IFN-lambda proteins can also induce Jak2 phosphorylation and activate other STAT family proteins, as well as MAPK signaling pathways. Type III IFNs have similar anti-viral, anti-proliferative, apoptotic, and immunomodulatory effects as the type I IFNs and typically induce a subset of the target genes that are induced by the type I IFN-alpha and IFN-beta proteins. As IL-28 R alpha/IFN-lambda R1 is primarily expressed on epithelial cells, it has been proposed that the type III IFNs may have specifically evolved to provide anti-viral protection at epithelial surfaces.

To learn more, please visit our IL-10/Interferon Family Research Area page

Type III Interferon Signaling Pathways background image 1