 Interferon Lambda Products
IL-28A, IL-28B and IL-29 are a recently discovered class II cytokine family that displays similar properties to type I
interferons (IFNs) (1, 2). Similarly, they
have been shown to function by
signaling through the JAK-STAT pathway
upregulating the expression of genes
involved in controlling viral replication
and cellular proliferation. Consequently,
they have also been described in the
literature as lambda IFNs (IFN-λ1[IL-29],
IFN-λ2 [IL-28A] and IFN-λ3 [IL-28B]) or
collectively as type III IFNs. Additional
studies have shown that both type I and
type III IFNs are upregulated during viral
infection suggesting each may have
similar and perhaps distinct roles in
controlling the host response to
pathogens (3).
All type III IFNs signal through a
heterodimer receptor complex comprised
of the IL-10R2 and the IL-28αR receptor
chains to initiate the signal transduction
cascade. In contrast, all the type I IFNs
(α, β, ε, κ, ω ) initiate signaling by
binding to the IFNAR1/IFNAR2 receptor
complex to promote signaling. IFNAR gene knock-out studies have indicated
type III IFNs cannot effectively
maintain a potent antiviral response. In
contrast, IL-28αR knockouts showed
little effect on the overall antiviral
response suggesting that the role of
type III interferons may be more selective to specific cells and viruses.
However, either receptor knock-out
showed a strong reduction in reducing
viral load when mice were treated with
TLR3 and TLR9 agonists (4). Therefore, it
may be possible that the type III IFNs
have been evolutionarily conserved to combat pathogens that target
specifically the IFNAR receptor complex
or other unique aspects of the classical
type I IFN pathways (5).
REFERENCES
1. Sheppard, P., et al. (2003). Nat. Immunol. 4:63-68
2. Kotenko, SV., et al. (2007). Nat. Immunol. 4:69-77
3. Onoguchi, K., et al. (2007). J. Immunol. 282:7576-7581
4. Ank, N., et al. (2008). J. Immunol. 180:2474-2485
5. Ank, N., et al. (2006). JICR. 26:373-379
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