Interferon (IFN) Family Proteins

Interferon (IFN) was first discovered in 1957 by Alick Isaacs and Jean Lindenmann from their initial studies in viral interference. Over the years, various studies about IFN were performed, elucidating its anti-viral activity. It was only until 1980 when IFN could be produced in a large-scale for research use, where pioneering recombinant DNA technology was utilized. IFN proteins were discovered to have both anti-tumor and immunomodulatory functions along with its inherent anti-viral activity, classifying them as a subset of cytokines.

The IFN protein family is organized into three types according to its corresponding receptor: type I, type II and type III; each of which are produced in different cellular locations. IFN-α and IFN-β are the most prominent members of type I IFNs and are mainly produced by pathogenesis-associated molecular patterns (PAMPs). PAMPs are induced by stimulation of Toll-like receptors (TLR) or cytoplasmic pattern recognition receptors located on the cell membrane. Type II IFNs have only one type, IFN-γ, which are produced by a variety of cells in the immune system. This includes innate lymphoid-like cell populations such as innate lymphocytes (ILC) and natural killer (NK) cells, as well as adaptive immune cells consisting of helper T cells 1 (Th1) and CD8 cytotoxic T lymphocytes (CTL). Type III IFNs are mainly produced by epithelial cells in non-hematopoietic cells, where viruses can mediate type III interferon expression in different cell types. However, since these IFNs were discovered in 2003, the exact mechanism of its production is still unknown and is the subject of various academic studies.

The corresponding signaling pathways of the three types of IFNs are also different, where each bind to different compositions of heterodimeric receptor complexes. Intracellular signaling is conducted through the Janus kinase/signal transducer and acts as an activator of transcription (JAK/STAT) pathways.