Abstract
IFNϵ and IFNκ are interferons that induce microbial immunity at mucosal surfaces and in the skin. They are members of the type-I interferon (IFN) family, which consists of 16 different IFNs, that all signal through the common IFNAR1/IFNAR2 receptor complex. Although IFNϵ and IFNκ have unique expression and functional properties, their biophysical properties have not been extensively studied. In this report, we describe the expression, purification, and characterization of recombinant human IFNϵ and IFNκ. In cellular assays, IFNϵ and IFNκ exhibit ∼1000-fold lower potency than IFNα2 and IFNω. The reduced potency of IFNϵ and IFNκ are consistent with their weak affinity for the IFNAR2 receptor chain. Despite reduced IFNAR2-binding affinities, IFNϵ and IFNκ exhibit affinities for the IFNAR1 chain that are similar to other IFN subtypes. As observed for cellular IFNAR2 receptor, the poxvirus antagonist, B18R, also exhibits reduced affinity for IFNϵ and IFNκ, relative to the other IFNs. Taken together, our data suggest IFNϵ and IFNκ are specialized IFNs that have evolved to weakly bind to the IFNAR2 chain, which allows innate protection of the mucosa and skin and limits neutralization of IFNϵ and IFNκ biological activities by viral IFN antagonists.
Highlights
IFN⑀ and IFN are interferons that induce microbial immunity at mucosal surfaces and in the skin
Endotoxin levels for IFN⑀ and IFN were less than 1 EU/g, which is within the range of values observed in IFN␣ preparations obtained from commercial sources [42]
MS was performed on the samples, which demonstrated the molecular masses were consistent with full-length IFN⑀ and IFN proteins without the N-terminal initiating methionine residues (Table 1)
Summary
Oped including the treatment of viral infections [17], cancer [18], and multiple sclerosis [19]. It appears that IFN⑀ appears to play an important role in immunity against HIV-1, IFN expression is rapidly reduced in keratinocytes that are infected with human papilloma virus strains that induce cervical cancer [41] These data strongly argue that IFN⑀ and IFN are essential components to the host response against pathogens in the FRT, whereas the specific role of IFN, produced by keratinocytes in the skin, remains to be determined. Despite a critical role of IFN⑀ and IFN signaling in mucosa and skin, their interactions with the IFNARs and their functional activities have not been extensively characterized To address this issue, we have expressed human IFN⑀ and IFN for comparative biophysical and functional studies with other IFN family members (often called IFN subtypes). Our data suggests IFN⑀ and IFN have evolved to exhibit reduced IFNAR2 binding affinity and biological potency optimized for tissue-specific expression and escape from viral type-I IFN antagonists
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