Interferons, interferon‐like cytokines, and their receptors

Abstract

Recombinant interferon-alpha (IFN-alpha) was approved by regulatory agencies in many countries in 1986. As the first biotherapeutic approved, IFN-alpha paved the way for the development of many other cytokines and growth factors. Nevertheless, understanding the functions of the multitude of human IFNs and IFN-like cytokines has just touched the surface. This review summarizes the history of the purification of human IFNs and the key aspects of our current state of knowledge of human IFN genes, proteins, and receptors. All the known IFNs and IFN-like cytokines are described [IFN-alpha, IFN-beta, IFN-epsilon, IFN-kappa, IFN-omega, IFN-delta, IFN-tau, IFN-gamma, limitin, interleukin-28A (IL-28A), IL-28B, and IL-29] as well as their receptors and signal transduction pathways. The biological activities and clinical applications of the proteins are discussed. An extensive section on the evolution of these molecules provides some new insights into the development of these proteins as major elements of innate immunity. The overall structure of the IFNs is put into perspective in relation to their receptors and functions.

Distinct evolution process among type I interferon in mammals

“…In the present study, an IFNδ-like gene in the human genome was identifi ed, refuting the concept that humans have no IFNδ genes (Pestka et al, 2004). This gene is located on chromosome 9, with a pseudogene named IFNA12p inside of it.…”

“…According to the receptors that they bind, IFNs can be divided into three types: type I, type II, and type III IFNs (Sheppard et al, 2003). There are many different kinds of type I IFNs, such as IFNα, β, δ, ε , ζ, κ, τ, and ω, but type II and type III IFNs are only by a single kind each, IFNγ and IFNλ, res pectively (Pestka et al, 2004).…”

Intronless and intron-containing type I IFN genes coexist in amphibian Xenopus tropicalis : Insights into the origin and evolution of type I IFNs in vertebrates

“…Type I IFNs are always regarded as the core IFN species since they have essential roles in limiting initial viral replications before effective humoral or cellular adaptive immune mechanisms become operational (Pestka et al, 2004;Teijaro, 2016), and evolutionary study on type I IFNs may shed light on the origin of antiviral immune response in vertebrates. It has been recently revealed in evolutionary and comparative immunology that introns were lost from primitive intron-containing type I IFN genes in fish and amphibians, and intronless type I IFN genes were evolved in amniotes (Chen et al, 2015;Goossens et al, 2013;Grayfer et al, 2014;Sang et al, 2014;Xu et al, 2013;Zou and Secombes, 2011;Zou et al, 2007); but it remains unclear how this process might have occurred (Zou et al, 2007).…”

“…Interferons (IFNs) are a group of cytokines playing crucial roles in immune defense in vertebrates (Pestka et al, 2004). According to sequence similarity, genomic structure, receptor usage and function, IFNs are divided into three types, i.e.…”

“…Functionally, type I and type III IFNs are specialized as innate antiviral cytokines (Lazear et al, 2015;Teijaro, 2016), whereas type II IFN is regarded as regulatory cytokine of both innate and adaptive immunity against viral and intracellular bacterial infection (Schoenborn and Wilson, 2007). Among the three types of IFNs, type I IFNs are considered to be the core IFN species because of their predominant antiviral effects (Pestka et al, 2004;Teijaro, 2016).…”