2008 PBL Cat_mech_r.qxd:PBL Catalog.mech 11/29/07 1:50 PM Page 4
Chapter 1: Interferons, Cytokines & Growth Factors
Interferon 101
Interferons (IFNs) are a family of mammalian cytokines initially characterized by their ability to inhibit viral
infection. In addition to their antiviral properties, IFNs have also been shown to exhibit antiproliferative,
immunomodulatory, and many other activities.
IFNs are classified as Type I or II based on receptor complex recognition and Like Receptors (TLR). The innate immune system has evolved the ability to
protein structure. Mammalian type I IFNs consist of over nine distinct recognize non-self motifs through the TLR receptors, e.g., double stranded
classes that include IFN-α, IFN-β, IFN-δ, IFN-ε, IFN-κ, IFN-ω, IFN-ν, IFN-τ and RNAs through TLR3, lipopolysaccharides through TLR4, and methylated CpG
IFN-ζ. While IFN-α, IFN-β, IFN-ε, IFN-κ, IFN-ω, and IFN-ν are found in DNA motifs through TLR9. Interferon produced by TLR-activated cells can
humans, IFN-δ, IFN-τ and IFN-ζ are not. These IFNs bind to the type I function in an autocrine or paracrine manner limiting pathogen infection.
receptor which is composed of two chains, commonly designated IFNAR1 When IFN interacts with its cognate receptor, a signal is rapidly transmitted
and IFNAR2. Type I IFNs are typically produced by macrophages, neutrophils, within the cell, often producing an antiviral state. The primary signal
dendritic cells and other somatic cells in response to many viruses and transduction cascade promoted by type I IFNs is the JAK1-STAT pathway (see
some pathogens . below).
In humans, IFN-α consists of a group of proteins that are greater than 85% Activation of this signal transduction pathway leads to increased gene
homologous by amino acid sequence. Only one human IFN-α is N- expression including (2’-5’) oligoadenylate synthetases, Mx proteins, and
glycosylated and a few IFN-αspecies have been shown to be O-glycosylated. protein kinase R (PKR) that protect the cell from viral infection. In fact, a host
In the mouse, nearly all of the IFN-α species are N-glycosylated. IFN-β, is of genes are expressed in response to interferons many of which have roles
produced by a variety of cells in response to viral challenge, and the native yet to be determined.
human IFN-β bears a single N-glycosylation site. The other type I IFNs have It remains unclear why there are so many different Type I IFNs including
not been studied extensively as IFN-α and IFN-β. Type II IFN in humans is multiple IFN-α subtypes. A variety of studies suggested they possess
limited to a single IFN-γgene. This IFN binds to the Type II receptor comprised overlapping but also unique sets of biological activities. Additional studies
of IFNGR1 (IFN-γR1) and IFNGR2 (IFN-γR2) chains. IFN-γ is produced by cells are revealing that type I IFNs may also play immunoregulatory roles. In
of the immune system such as T-cells and NK cells. IFN-γ is glycosylated in contrast, the primary role of IFN-γ is the activation and development of
mammalian cells, and functions as a homodimer. On a mass basis, IFN-αand adaptive immune functions with a lesser role in innate immune responses.
IFN-β exhibit more potent antiviral activity than IFN-γ. Despite over fifty years of intense research, there are still many unanswered
Often, the expression of the type I IFNs is induced by engagement of Toll- questions regarding interferons.
TYPE I INTERFERON RECEPTOR COMPLEX
IFN-αR1
IFN−α
IFN-αR2c
Ligand Binding
IFN−α
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2
γ
k
2
J
a
k
1
γ
T
T J
a
k
1
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2
a
t
t
2
St
1
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St
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St
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p48
transcription
ISRE
PBLInterferonSource Toll Free: 1 877- PBL-8881
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