Interleukin 28: Difference between revisions

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__NOTOC__
{{infobox protein
{{protein
| Name = Interleukin 28A
| Name = Interleukin 28A
| caption =  
| caption =  
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| HGNCid = 18364
| HGNCid = 18364
| Symbol = IL28A
| Symbol = IL28A
| AltSymbols = , IFNL2
| AltSymbols = IFNL2
| EntrezGene = 282616
| EntrezGene = 282616
| OMIM = 607401
| OMIM = 607401
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| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
{{protein
{{infobox protein
| Name = Interleukin 28B
| Name = Interleukin 28B
| caption =  
| caption =  
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| HGNCid = 18365
| HGNCid = 18365
| Symbol = IL28B
| Symbol = IL28B
| AltSymbols = , IFNL3
| AltSymbols = IFNL3
| EntrezGene = 282617
| EntrezGene = 282617
| OMIM = 607402
| OMIM = 607402
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| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
{{SI}}
{{CMG}}; {{AE}} {{VR}}


==Overview==
'''Interleukin-28''' (IL-28) is a [[cytokine]] that comes in two [[isoform]]s, IL-28A and IL-28B, and plays a role in immune defense against [[virus]]es, including the induction of an "antiviral state" by turning on Mx proteins, [[OAS1|2',5'-oligoadenylate synthetase]] as well as [[ISGF3G]] (Interferon Stimulated Gene Factor 3).<ref name="pmid15171810">{{cite journal |vauthors=Kempuraj D, Donelan J, Frydas S, Iezzi T, Conti F, Boucher W, Papadopoulou NG, Madhappan B, Letourneau L, Cao J, Sabatino G, Meneghini F, Stellin L, Verna N, Riccioni G, Theoharides TC | title = Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities | journal = Int J Immunopathol Pharmacol | volume = 17 | issue = 2 | pages = 103–6 | year = 2004 | pmid = 15171810 | doi = | url = }}</ref> IL-28A and IL-28B belong to the [[type III interferon|type III]] [[interferon]] family of cytokines and are highly similar (in [[amino acid]] sequence) to [[interleukin 29|IL-29]].  Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are.
Interleukin-28 (IL-28) is a [[cytokine]] that comes in two [[isoform]]s, IL-28A and IL-28B, and plays a role in immune defense against [[virus]]es.<ref name="Kempuraj-">{{Cite journal | last1 = Kempuraj | first1 = D. | last2 = Donelan | first2 = J. | last3 = Frydas | first3 = S. | last4 = Iezzi | first4 = T. | last5 = Conti | first5 = F. | last6 = Boucher | first6 = W. | last7 = Papadopoulou | first7 = NG. | last8 = Madhappan | first8 = B. | last9 = Letourneau | first9 = L. | title = Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities. | journal = Int J Immunopathol Pharmacol | volume = 17 | issue = 2 | pages = 103-6 | month = | year = | doi = | PMID = 15171810 }}</ref> IL-28A and IL-28B belong to the [[Interferon type III|type III interferon]] family of cytokines and are highly similar (in [[amino acid]] sequence) to [[interleukin 29|IL-29]].  IL-28 [[gene]]s are located near IL-29 on [[chromosome 19]] in humans.  


==Historical Perspective==
== Discovery ==
IL-28 was discovered in 2003 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes.<ref name="pmid12469119">{{cite journal | author = Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM | title = IL-28, IL-29 and their class II cytokine receptor IL-28R | journal = Nat. Immunol. | volume = 4 | issue = 1 | pages = 63–8 | year = 2003 | month = January | pmid = 12469119 | doi = 10.1038/ni873 | url =  }}</ref>  Once these genes were found, a second scan was performed to look specifically for cytokines.  Both IL-28 and IL-29 were found in humans using this type of analysis.


==Structure==
IL-28 was discovered in 2002 by Zymogenetics<ref name="pmid12469119">{{cite journal |vauthors=Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM | title = IL-28, IL-29 and their class II cytokine receptor IL-28R | journal = Nat. Immunol. | volume = 4 | issue = 1 | pages = 63–8 |date=January 2003 | pmid = 12469119 | doi = 10.1038/ni873 | url = }}</ref> using a genomic screening process in which the entire human genome was scanned for putative genes.  Once these genes were found, a second scan was performed to look specifically for cytokines.  Both IL-28 and IL-29 were found in humans using this type of analysis.
IL-28 [[gene]]s are located near IL-29 on [[chromosome 19]] in humans.  The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous.  Differences in function between the two forms remains unclear.  The receptor for IL-28 is composed of a unique IL-28 receptor alpha chain which pairs with the IL-10 receptor beta chain, leading many to classify IL-28 as a IL-10-like family member.


==Function==
== Structure ==
IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.<ref name="pmid19304955">{{cite journal | author = Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB | title = Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity | journal = Blood | volume = 113 | issue = 23 | pages = 5868–77 | year = 2009 | month = June | pmid = 19304955 | doi = 10.1182/blood-2008-11-190520 | url = | pmc = 2700323 }}</ref>


== Clinical Significance ==
IL-28 [[gene]]s are located near IL-29 on [[chromosome 19]] in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous. Differences in function between the two forms remains unclear.
Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28.<ref name="pmid19304955" /> Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study.<ref name="pmid20571540">{{cite journal | author = Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB. | title = IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques | journal = Molecular Therpay | volume = 18 | issue = 9 | pages = 1714–23 | year = 2010 | month = Sep | pmid = 20571540 | doi = 10.1038/mt.2010.118 | url = | pmc = 2956930 }}</ref> A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to [[hepatitis C]] treatment with [[interferon]] and [[ribavirin]], and high [[LDL]] levels.<ref>{{cite journal |author=Ge D, Fellay j, Thompson A, ''et al.'' |title=Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance |journal=Nature |year=2009 |doi=10.1038/nature08309 |pmid=19684573 |volume=461 |issue=7262 |pages=399–401}}</ref><ref name="Clark-2012">{{Cite journal | last1 = Clark | first1 = PJ. | last2 = Thompson | first2 = AJ. | last3 = Zhu | first3 = M. | last4 = Vock | first4 = DM. | last5 = Zhu | first5 = Q. | last6 = Ge | first6 = D. | last7 = Patel | first7 = K. | last8 = Harrison | first8 = SA. | last9 = Urban | first9 = TJ. | title = Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response. | journal = J Viral Hepat | volume = 19 | issue = 5 | pages = 332-40 | month = May | year = 2012 | doi = 10.1111/j.1365-2893.2011.01553.x | PMID = 22497812 }}</ref> The SNP was identified in a [[genome-wide association study]] (GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.<ref>{{cite journal|last=Maxmen|first=Amy|title=Pharmacogenomics: Playing the odds|journal=Nature|date=NaN undefined NaN|volume=474|issue=7350|pages=S9–S10|doi=10.1038/474S9a|pmid=21666735}}</ref>
 
The receptor for IL-28 is composed of a unique IL-28 Receptor Alpha chain which pairs with the IL-10 Receptor Beta chain, leading many to classify IL-28 as an IL-10-like family member.
 
== Function ==
 
IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.<ref name="pmid19304955">{{cite journal |vauthors=Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB | title = Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity | journal = Blood | volume = 113 | issue = 23 | pages = 5868–77 |date=June 2009 | pmid = 19304955 | doi = 10.1182/blood-2008-11-190520 | url = | pmc = 2700323 }}</ref>
 
== Clinical significance ==
 
Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28.<ref name="pmid19304955" />
 
Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study.<ref name="pmid20571540">{{cite journal |vauthors=Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB | title = IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques | journal = Molecular Therapy | volume = 18 | issue = 9 | pages = 1714–23 |date=Sep 2010 | pmid = 20571540 | doi = 10.1038/mt.2010.118 | url = | pmc = 2956930 }}</ref> Scientists have credited this link to explain why some people infected with HSV-1 experience cold sores, while others do not.
 
A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to [[hepatitis C]] treatment with [[interferon]] and [[ribavirin]].<ref>{{cite web|url=http://www.pgxnews.org/web/pgx-pharmacogenomics-articles-reviews/40-pgx-pharmacogenomics-article-review/104-new-biomarker-predicts-response-to-hepatitis-c-treatment |title=New biomarker predicts response to hepatitis C treatment |author=PGxNews.Org |publisher=PGxNews.Org |accessdate=2009-08-17 |date=August 2009 |deadurl=yes |archiveurl=https://web.archive.org/web/20091121121037/http://www.pgxnews.org/web/pgx-pharmacogenomics-articles-reviews/40-pgx-pharmacogenomics-article-review/104-new-biomarker-predicts-response-to-hepatitis-c-treatment |archivedate=November 21, 2009 }}</ref><ref>{{cite journal |author1=Ge D |author2=Fellay j |author3=Thompson A |title=Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance |journal=Nature |year=2009 |doi=10.1038/nature08309 |pmid=19684573 |volume=461 |issue=7262 |pages=399–401|display-authors=etal}}</ref> The SNP was identified in a [[genome-wide association study]] (GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.<ref>{{cite journal|last=Maxmen|first=Amy|title=Pharmacogenomics: Playing the odds|journal=Nature|volume=474|issue=7350|pages=S9–S10|doi=10.1038/474S9a|pmid=21666735}}</ref>


== References ==
== References ==
{{Reflist|2}}
{{reflist|30em}}
 
{{interleukins}}
{{Interferons}}


[[Category:Cytokines]]
{{Interleukins}}
{{Interleukin receptor modulators}}


{{WH}}
[[Category:Interleukins]]
{{WS}}

Latest revision as of 17:14, 1 August 2017

Interleukin 28A
Identifiers
SymbolIL28A
Alt. symbolsIFNL2
Entrez282616
HUGO18364
OMIM607401
RefSeqNM_172138
UniProtQ8IZJ0
Other data
LocusChr. 19 q13.13
Interleukin 28B
Identifiers
SymbolIL28B
Alt. symbolsIFNL3
Entrez282617
HUGO18365
OMIM607402
RefSeqNM_172139
UniProtQ8IZI9
Other data
LocusChr. 19 q13.13

Interleukin-28 (IL-28) is a cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses, including the induction of an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as ISGF3G (Interferon Stimulated Gene Factor 3).[1] IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in amino acid sequence) to IL-29. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are.

Discovery

IL-28 was discovered in 2002 by Zymogenetics[2] using a genomic screening process in which the entire human genome was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and IL-29 were found in humans using this type of analysis.

Structure

IL-28 genes are located near IL-29 on chromosome 19 in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous. Differences in function between the two forms remains unclear.

The receptor for IL-28 is composed of a unique IL-28 Receptor Alpha chain which pairs with the IL-10 Receptor Beta chain, leading many to classify IL-28 as an IL-10-like family member.

Function

IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.[3]

Clinical significance

Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28.[3]

Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study.[4] Scientists have credited this link to explain why some people infected with HSV-1 experience cold sores, while others do not.

A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C treatment with interferon and ribavirin.[5][6] The SNP was identified in a genome-wide association study (GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.[7]

References

  1. ↑ Kempuraj D, Donelan J, Frydas S, Iezzi T, Conti F, Boucher W, Papadopoulou NG, Madhappan B, Letourneau L, Cao J, Sabatino G, Meneghini F, Stellin L, Verna N, Riccioni G, Theoharides TC (2004). "Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities". Int J Immunopathol Pharmacol. 17 (2): 103–6. PMID 15171810.
  2. ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (January 2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nat. Immunol. 4 (1): 63–8. doi:10.1038/ni873. PMID 12469119.
  3. ↑ 3.0 3.1 Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB (June 2009). "Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity". Blood. 113 (23): 5868–77. doi:10.1182/blood-2008-11-190520. PMC 2700323. PMID 19304955.
  4. ↑ Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB (Sep 2010). "IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques". Molecular Therapy. 18 (9): 1714–23. doi:10.1038/mt.2010.118. PMC 2956930. PMID 20571540.
  5. ↑ PGxNews.Org (August 2009). "New biomarker predicts response to hepatitis C treatment". PGxNews.Org. Archived from the original on November 21, 2009. Retrieved 2009-08-17.
  6. ↑ Ge D; Fellay j; Thompson A; et al. (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. doi:10.1038/nature08309. PMID 19684573.
  7. ↑ Maxmen, Amy. "Pharmacogenomics: Playing the odds". Nature. 474 (7350): S9–S10. doi:10.1038/474S9a. PMID 21666735.
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