“Interferon type I”的意思、由来-开放百科全书

Human type I interferons (IFNs) are a large subgroup of interferon proteins that help regulate the activity of the immune system.

Interferons bind to interferon receptors. All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.

Type I IFNs are found in all mammals, and homologous (similar) molecules have been found in birds, reptiles, amphibians and fish species.^[1]^[2]

Mammalian types

The mammalian types are designated IFN-α (alpha), IFN-β (beta), IFN-κ (kappa), IFN-δ (delta), IFN-ε (epsilon), IFN-τ (tau), IFN-ω (omega), and IFN-ζ (zeta, also known as limitin).^[3]^[4]

IFN-α

The IFN-α proteins are produced mainly by plasmacytoid dendritic cells (pDCs). They are mainly involved in innate immunity against viral infection. The genes responsible for their synthesis come in 13 subtypes that are called IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21. These genes are found together in a cluster on chromosome 9.

IFN-α is also made synthetically as medication in hairy cell leukemia. The International Nonproprietary Name (INN) for the product is interferon alfa. The recombinant type is interferon alfacon-1. The pegylated types are pegylated interferon alfa-2a and pegylated interferon alfa-2b.

IFN-β

The IFN-β proteins are produced in large quantities by fibroblasts. They have antiviral activity that is involved mainly in innate immune response. Two types of IFN-β have been described, IFN-β1 (IFNB1) and IFN-β3 (IFNB3)^[5] (a gene designated IFN-β2 is actually IL-6). IFN-β1 is used as a treatment for multiple sclerosis as it reduces the relapse rate.

IFN-β1 is not an appropriate treatment for patients with progressive, non-relapsing forms of multiple sclerosis.^[6]

IFN-ε, -κ, -τ, -δ and -ζ

IFN-ε, -κ, -τ, and -ζ appear, at this time, to come in a single isoform in humans, IFNK. Only ruminants encode IFN-τ, a variant of IFN-ω. So far, IFN-ζ is only found in mice, while a structural homolog, IFN-δ is found in a diverse array of non-primate and non-rodent placental mammals. Most but not all placental mammals encode functional IFN-ε and IFN-κ genes.

IFN-ω

IFN-ω, although having only one functional form described to date (IFNW1), has several pseudogenes: {{Gene|IFNWP2}}, {{Gene|IFNWP4}}, {{Gene|IFNWP5}}, {{Gene|IFNWP9}}, {{Gene|IFNWP15}}, {{Gene|IFNWP18}}, and {{Gene|IFNWP19}} in humans. Many non-primate placental mammals express multiple IFN-ω subtypes.

IFN-ν

This subtype of type I IFN was recently described as a pseudogene in human, but potentially functional in the domestic cat genome. In all other genomes of non-feline placental mammals, IFN-ν is a pseudogene; in some species, the pseudogene is well preserved, while in others, it is badly mutilated or is undetectable. Moreover, in the cat genome, the IFN-ν promoter is deleteriously mutated. It is likely that the IFN-ν gene family was rendered useless prior to mammalian diversification. Its presence on the edge of the type I IFN locus in mammals may have shielded it from obliteration, allowing its detection.

Sources and functions

IFN-α and IFN-β are secreted by many cell types including lymphocytes (NK cells, B-cells and T-cells), macrophages, fibroblasts, endothelial cells, osteoblasts and others. They stimulate both macrophages and NK cells to elicit an anti-viral response, involving IRF3/IRF7 antiviral pathways,^[7] and are also active against tumors. Plasmacytoid dendritic cells have been identified as being the most potent producers of type I IFNs in response to antigen, and have thus been coined natural IFN producing cells.

IFN-α acts as a pyrogenic factor by altering the activity of thermosensitive neurons in the hypothalamus thus causing fever. It does this by binding to opioid receptors and eliciting the release of prostaglandin-E₂ (PGE₂).

A similar mechanism is used by IFN-α to reduce pain; IFN-α interacts with the μ-opioid receptor to act as an analgesic.^[8]

In mice, IFN-β inhibits immune cell production of growth factors, thereby slowing tumor growth, and inhibits other cells from producing vessel producing growth factors, thereby blocking tumor angiogenesis and hindering the tumour from connecting into the blood vessel system.^[9]

In both mice and human, negative regulation of type I interferon is known to be important. Few endogenous regulators have been found to elicit this important regulatory function, such as SOCS1 and Aryl Hydrocarbon Receptor Interacting Protein (AIP).^[10]

Non-mammalian types

Avian type I IFNs have been characterized and preliminarily assigned to subtypes (IFN I, IFN II, and IFN III), but their classification into subtypes should await a more extensive characterization of avian genomes.

Turtle type I IFNs have been purified (references from 1970s needed). They resemble mammalian homologs.

The existence of amphibian type I IFNs have been inferred by the discovery of the genes encoding their receptor chains. They have not yet been purified, or their genes cloned.

Piscine (bony fish) type I IFN has been cloned first in zebrafish.^[11]^[12] and then in many other teleost species including salmon and mandarin fish.^[13]^[14] With few exceptions, and in stark contrast to avian and especially mammalian IFNs, they are present as single genes (multiple genes are however seen in polyploid fish genomes, possibly arising from whole-genome duplication). Unlike amniote IFN genes, piscine type I IFN genes contain introns, in similar positions as do their orthologs, certain interleukins. Despite this important difference, based on their 3-D structure these piscine IFNs have been assigned as Type I IFNs.^[15] While in mammalian species all Type I IFNs bind to a single receptor complex, the different groups of piscine type I IFNs bind to different receptor complexes.^[16]. Until now several type I IFNs (IFNa, b, c, d, e, f and h)

has been identified in teleost fish with as low as only one subtype in green pufferfish and as many as six subtypes in salmon with an addition of recently identified novel subtype, IFNh in mandarin fish. ^[17]^[18].

References

1. ^{{cite journal | vauthors = Schultz U, Kaspers B, Staeheli P | title = The interferon system of non-mammalian vertebrates | journal = Developmental and Comparative Immunology | volume = 28 | issue = 5 | pages = 499–508 | date = May 2004 | pmid = 15062646 | doi = 10.1016/j.dci.2003.09.009 }}
2. ^{{cite book | editor =Meager A | title = The interferons: characterization and application | year = 2006 | publisher = Wiley-VCH | location = Weinheim | isbn = 978-3-527-31180-4 |vauthors=Samarajiwa SA, Wilson W, Hertzog PJ | chapter = Type I interferons: genetics and structure | pages = 3–34 }}
3. ^{{cite journal | vauthors = Oritani K, Tomiyama Y | title = Interferon-zeta/limitin: novel type I interferon that displays a narrow range of biological activity | journal = International Journal of Hematology | volume = 80 | issue = 4 | pages = 325–31 | date = November 2004 | pmid = 15615256 | doi = 10.1532/ijh97.04087 }}
4. ^{{cite journal | vauthors = Hardy MP, Owczarek CM, Jermiin LS, Ejdebäck M, Hertzog PJ | title = Characterization of the type I interferon locus and identification of novel genes | journal = Genomics | volume = 84 | issue = 2 | pages = 331–45 | date = August 2004 | pmid = 15233997 | doi = 10.1016/j.ygeno.2004.03.003 }}
5. ^{{cite journal | vauthors = Todd S, Naylor SL | title = New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene | journal = Somatic Cell and Molecular Genetics | volume = 18 | issue = 4 | pages = 381–5 | date = July 1992 | pmid = 1440058 | doi = 10.1007/BF01235761 }}
6. ^{{Citation |author1 = American Academy of Neurology |author1-link = American Academy of Neurology |date=February 2013 |title = Five Things Physicians and Patients Should Question |publisher = American Academy of Neurology |work = Choosing Wisely: an initiative of the ABIM Foundation |page = |url = http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-neurology/ |access-date = August 1, 2013}}, which cites*{{citation| vauthors = La Mantia L, Vacchi L, Di Pietrantonj C, Ebers G, Rovaris M, Fredrikson S, Filippini G | title = Cochrane Database of Systematic Reviews | volume = 1 | pages = CD005181 | year = 2012 | pmid = 22258960 | pmc = | doi = 10.1002/14651858.CD005181.pub3 | chapter = Interferon beta for secondary progressive multiple sclerosis | editor1-last = La Mantia | editor1-first = Loredana }}*{{citation | vauthors = Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E | title = Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006643 | year = 2010 | pmid = 20091602 | pmc = | doi = 10.1002/14651858.CD006643.pub3 | chapter = Interferon Beta for Primary Progressive Multiple Sclerosis | editor1-last = Rojas | editor1-first = Juan Ignacio | name-list-format = vanc }}
7. ^{{cite journal | vauthors = Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW | title = Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon | journal = The Journal of Biological Chemistry | volume = 290 | issue = 23 | pages = 14729–39 | date = June 2015 | pmid = 25911105 | pmc = 4505538 | doi = 10.1074/jbc.M114.633065 }}
8. ^{{cite journal | vauthors = Wang YX, Xu WG, Sun XJ, Chen YZ, Liu XY, Tang H, Jiang CL | title = Fever of recombinant human interferon-alpha is mediated by opioid domain interaction with opioid receptor inducing prostaglandin E2 | journal = Journal of Neuroimmunology | volume = 156 | issue = 1-2 | pages = 107–12 | date = November 2004 | pmid = 15465601 | doi = 10.1016/j.jneuroim.2004.07.013 }}
9. ^{{cite journal | vauthors = Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S | title = Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model | journal = The Journal of Clinical Investigation | volume = 120 | issue = 4 | pages = 1151–64 | date = April 2010 | pmid = 20237412 | pmc = 2846036 | doi = 10.1172/JCI37223 | laysummary = http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/the_immune_systems_guard_against_cancer/ | laysource = Helmholtz Centre for Infection Research }}
10. ^{{cite journal | vauthors = Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW | title = Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1 | journal = Journal of Virology | volume = 85 | issue = 14 | pages = 6955–62 | date = July 2011 | pmid = 21593151 | pmc = 3126571 | doi = 10.1128/JVI.00007-11 }}
11. ^{{cite journal | vauthors = Altmann SM, Mellon MT, Distel DL, Kim CH | title = Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerio | journal = Journal of Virology | volume = 77 | issue = 3 | pages = 1992–2002 | date = February 2003 | pmid = 12525633 | pmc = 140984 | doi = }}
12. ^{{cite journal | vauthors = Lutfalla G, Roest Crollius H, Stange-Thomann N, Jaillon O, Mogensen K, Monneron D | title = Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: the class II cytokine receptors and their ligands in mammals and fish | journal = BMC Genomics | volume = 4 | issue = 1 | pages = 29 | date = July 2003 | pmid = 12869211 | pmc = 179897 | doi = 10.1186/1471-2164-4-29 }}
13. ^{{cite journal | vauthors = Laghari ZA, Chen SN, Li L, Huang B, Gan Z, Zhou Y, Huo HJ, Hou J, Nie P | title = Functional, signalling and transcriptional differences of three distinct type I IFNs in a perciform fish, the mandarin fish Siniperca chuatsi | journal = Developmental and Comparative Immunology | volume = 84 | issue = 1 | pages = 94–108 | date = July 2018 | pmid = 29432791 | doi = 10.1016/j.dci.2018.02.008 }}
14. ^{{cite journal | vauthors = Boudinot P, Langevin C, Secombes CJ, Levraud JP | title = The Peculiar Characteristics of Fish Type I Interferons | journal = Viruses | volume = 8 | issue = 11 | date = November 2016 | pmid = 27827855 | pmc = 5127012 | doi = 10.3390/v8110298 }}
15. ^{{cite journal | vauthors = Hamming OJ, Lutfalla G, Levraud JP, Hartmann R | title = Crystal structure of Zebrafish interferons I and II reveals conservation of type I interferon structure in vertebrates | journal = Journal of Virology | volume = 85 | issue = 16 | pages = 8181–7 | date = August 2011 | pmid = 21653665 | pmc = 3147990 | doi = 10.1128/JVI.00521-11 }}
16. ^{{cite journal | vauthors = Aggad D, Mazel M, Boudinot P, Mogensen KE, Hamming OJ, Hartmann R, Kotenko S, Herbomel P, Lutfalla G, Levraud JP | title = The two groups of zebrafish virus-induced interferons signal via distinct receptors with specific and shared chains | journal = Journal of Immunology | volume = 183 | issue = 6 | pages = 3924–31 | date = September 2009 | pmid = 19717522 | doi = 10.4049/jimmunol.0901495 }}
17. ^{{cite journal | vauthors = Laghari ZA, Chen SN, Li L, Huang B, Gan Z, Zhou Y, Huo HJ, Hou J, Nie P | title = Functional, signalling and transcriptional differences of three distinct type I IFNs in a perciform fish, the mandarin fish Siniperca chuatsi | journal = Developmental and Comparative Immunology | volume = 84 | issue = 1 | pages = 94–108 | date = July 2018 | pmid = 29432791 | doi = 10.1016/j.dci.2018.02.008 }}
18. ^{{cite journal | vauthors = Boudinot P, Langevin C, Secombes CJ, Levraud JP | title = The Peculiar Characteristics of Fish Type I Interferons | journal = Viruses | volume = 8 | issue = 11 | date = November 2016 | pmid = 27827855 | pmc = 5127012 | doi = 10.3390/v8110298 }}