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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
{{Infobox_gene}}
'''Interleukin 9''', also known as '''IL-9''', is a [[Pleiotropy|pleiotropic]] [[cytokine]] (cell signalling molecule) belonging to the group of [[interleukin]]s.<ref name="entrez">{{cite web | title = Entrez Gene: IL9 interleukin 9| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3578| accessdate = }}</ref>IL-9 is produced by variety of cells like [[mast cell]]<nowiki/>s, [[Natural killer T cell|NKT]] cells, [[T helper cell|Th2]], [[T helper 17 cell|Th17]], [[Regulatory T cell|Treg]], [[ILC2]], and Th9 cells in different amounts. Among them, [[T helper cell|Th9 cell]]<nowiki/>s are regarded as the major [[CD4+ helper cells|CD4+ T cells]] that produce IL-9.<ref>{{cite journal | vauthors = Rojas-Zuleta WG, Sanchez E | title = IL-9: Function, Sources, and Detection | journal = Methods in Molecular Biology | volume = 1585 | pages = 21–35 | date = 2017 | pmid = 28477184 | doi = 10.1007/978-1-4939-6877-0_2 }}</ref>
'''Interleukin 9''', also known as '''IL-9''', is a [[Pleiotropy|pleiotropic]] [[cytokine]] (cell signalling molecule) belonging to the group of [[interleukin]]s.<ref name="entrez">{{cite web | title = Entrez Gene: IL9 interleukin 9| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3578}}</ref> IL-9 is produced by variety of cells like [[mast cell]]s, [[Natural killer T cell|NKT]] cells, [[T helper cell|Th2]], [[T helper 17 cell|Th17]], [[Regulatory T cell|Treg]], [[ILC2]], and Th9 cells in different amounts. Among them, [[T helper cell|Th9 cells]] are regarded as the major [[CD4+ helper cells|CD4+ T cells]] that produce IL-9.<ref name="ReferenceA">{{cite book | vauthors = Rojas-Zuleta WG, Sanchez E | title = Th9 Cells | chapter = IL-9: Function, Sources, and Detection | series = Methods in Molecular Biology | volume = 1585 | pages = 21–35 | date = 2017 | pmid = 28477184 | doi = 10.1007/978-1-4939-6877-0_2 | isbn = 978-1-4939-6876-3 | hdl = 10161/14730 }}</ref>


== Function ==
== Functions ==


Il-9 is a [[cytokine]] secreted by [[CD4+ helper cells]] that acts as a regulator of a variety of [[hematopoietic cell]]s.<ref name="pmid21371941">{{cite journal | vauthors = Perumal NB, Kaplan MH | title = Regulating IL9 transcription in T helper cells | journal = Trends in Immunology | volume = 32 | issue = 4 | pages = 146–50 | year = 2011 | pmid = 21371941 | pmc = 3070825 | doi = 10.1016/j.it.2011.01.006 }}</ref> This cytokine stimulates [[cell proliferation]] and prevents [[apoptosis]]. It functions through the [[interleukin-9 receptor]] (IL9R), which activates different signal transducer and activator ([[STAT protein|STAT]]) proteins and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for [[asthma]]. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of [[bronchial hyperresponsiveness]].<ref name="entrez" />
Il-9 is a [[cytokine]] secreted by [[CD4+ helper cells]] that acts as a regulator of a variety of [[hematopoietic cell]]s.<ref name="pmid21371941">{{cite journal | vauthors = Perumal NB, Kaplan MH | title = Regulating IL9 transcription in T helper cells | journal = Trends in Immunology | volume = 32 | issue = 4 | pages = 146–50 | year = 2011 | pmid = 21371941 | pmc = 3070825 | doi = 10.1016/j.it.2011.01.006 }}</ref> This cytokine stimulates [[cell proliferation]] and prevents [[apoptosis]]. It functions through the [[interleukin-9 receptor]] (IL9R), which activates different signal transducer and activator ([[STAT protein|STAT]]) proteins namely [[STAT1]], [[STAT3]] and [[STAT5]] and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for [[asthma]]. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of [[bronchial hyperresponsiveness]].<ref name="entrez" />


Interleukin-9 has also shown to inhibit [[melanoma]] growth in mice.<ref name="pmid22772464">{{cite journal | vauthors = Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS | title = Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells | journal = Nature Medicine | volume = 18 | issue = 8 | pages = 1248–53 | date = August 2012 | pmid = 22772464 | pmc = 3518666 | doi = 10.1038/nm.2856 | laysummary = http://medicalxpress.com/news/2012-07-scientists-molecule-immune-dangerous-skin.html | laysource = medicalxpress.com }}</ref>
Interleukin-9 has also shown to inhibit [[melanoma]] growth in mice.
<ref name="pmid22772464">{{cite journal | vauthors = Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS | title = Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells | journal = Nature Medicine | volume = 18 | issue = 8 | pages = 1248–53 | date = August 2012 | pmid = 22772464 | pmc = 3518666 | doi = 10.1038/nm.2856 }}
*{{lay source |template = cite web|url = https://medicalxpress.com/news/2012-07-scientists-molecule-immune-dangerous-skin.html|title = Scientists find molecule in immune system that could help treat dangerous skin cancer|date = July 8, 2012 |website = MedicalXpress }}</ref>


Additionally, it gives rise to the multiplication of [[Hematologic neoplasms|hematologic neoplasias]] and also [[Hodgkin's lymphoma]] in humans but IL-9 also has antitumor properties in solid tumors,for example [[melanoma]].<ref>{{cite journal | vauthors = Rojas-Zuleta WG, Sanchez E | title = IL-9: Function, Sources, and Detection | journal = Methods in Molecular Biology | volume = 1585 | pages = 21–35 | date = 2017 | pmid = 28477184 | doi = 10.1007/978-1-4939-6877-0_2 }}</ref>
Additionally, it gives rise to the multiplication of [[Hematologic neoplasms|hematologic neoplasias]] and also [[Hodgkin's lymphoma]] in humans but IL-9 also has antitumor properties in solid tumors, for example [[melanoma]].<ref name="ReferenceA"/>


== Discovery & History ==
== Discovery ==
IL-9 was first described in the late 1980s as a member of a growing number of [[cytokines]] that had [[Pleiotropy|pleiotropic]] functions in the [[immune]] system.IL-9 remains an understudied cytokine even though it has been allocated with many biological functions.It was first purified and characterized as a [[T cell]] and [[mast cell]] growth factor and termed as P40, based on their [[Molecular Weight|molecular weight]], or Mast cell growth-enhancing activity (MEA).The [[cloning]] and complete [[amino acid]] sequencing of P40 disclosed that it is structurally different from other [[T cell]]<nowiki/>s growth factors. So, it was named IL-9 based on its biological effects on both [[Myeloid cells|myeloid]] and [[Lymphoid cells|lymphoid]] cells.<ref>{{Cite journal|last=Goswami|first=Ritobrata|last2=Kaplan|first2=Mark H.|date=2011-03-15|title=A Brief History of IL-9|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074408/|journal=Journal of immunology (Baltimore, Md. : 1950)|volume=186|issue=6|pages=3283–3288|doi=10.4049/jimmunol.1003049|issn=0022-1767|pmc=PMC3074408|pmid=21368237}}</ref>
IL-9 was first described in the late 1980s as a member of a growing number of [[cytokines]] that had [[Pleiotropy|pleiotropic]] functions in the [[immune]] system.IL-9 remains an understudied cytokine even though it has been allocated with many biological functions. It was first purified and characterized as a [[T cell]] and [[mast cell]] growth factor and termed as P40, based on their [[Molecular Weight|molecular weight]], or Mast cell growth-enhancing activity (MEA).The [[cloning]] and complete [[amino acid]] sequencing of P40 disclosed that it is structurally different from other [[T cell]]s growth factors. So, it was named IL-9 based on its biological effects on both [[Myeloid cells|myeloid]] and [[Lymphoid cells|lymphoid]] cells.<ref>{{cite journal | vauthors = Goswami R, Kaplan MH | title = A brief history of IL-9 | journal = Journal of Immunology | volume = 186 | issue = 6 | pages = 3283–8 | date = March 2011 | pmid = 21368237 | pmc = 3074408 | doi = 10.4049/jimmunol.1003049 }}</ref>


The identification and [[cloning]] was first done by Yang and colleagues as a [[mitogenic factor]] for a human megakaryoblastic leukemia. The same human [[cDNA]] was isolated again by cross-hybridization with the mouse IL-9 probe.<ref name="Renauld 1995 287–303">{{cite book|title=Cytokines: Interleukins and Their Receptors|volume = 80|last=Renauld|first=Jean-Christophe |date=1995|publisher=Springer, Boston, MA|isbn=9781461285281|series=Cancer Treatment and Research|pages=287–303|language=en|doi=10.1007/978-1-4613-1241-3_11|chapter = Interleukin-9: Structural characteristics and biologic properties|pmid = 8821582}}</ref>
⚫
== Production of IL-9 ==

⚫
[[Interleukin 33]] (IL-33) induces IL-9 expression and secretion in [[T cell]]<nowiki/>s, which was confirmed by the results obtained in mice by using Human [[In vitro|''in vitro'']]<nowiki/>system.<ref>{{Cite journal|last=Humphreys|first=Neil E.|last2=Xu|first2=Damo|last3=Hepworth|first3=Matthew R.|last4=Liew|first4=Foo Y.|last5=Grencis|first5=Richard K.|date=2008-02-15|title=IL-33, a potent inducer of adaptive immunity to intestinal nematodes|url=https://www.ncbi.nlm.nih.gov/pubmed/18250453|journal=Journal of Immunology (Baltimore, Md.: 1950)|volume=180|issue=4|pages=2443–2449|issn=0022-1767|pmid=18250453}}</ref> Whereas the report of others confirms that [[TGF-b|TGF-β]] is a essential factor for IL-9 induction.<ref>{{Cite journal|last=Beriou|first=Gaëlle|last2=Bradshaw|first2=Elizabeth M.|last3=Lozano|first3=Ester|last4=Costantino|first4=Cristina M.|last5=Hastings|first5=William D.|last6=Orban|first6=Tihamer|last7=Elyaman|first7=Wassim|last8=Khoury|first8=Samia J.|last9=Kuchroo|first9=Vijay K.|date=2010-07-01|title=TGF-β Induces IL-9 Production from Human Th17 Cells|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936106/|journal=Journal of immunology (Baltimore, Md. : 1950)|volume=185|issue=1|pages=46–54|doi=10.4049/jimmunol.1000356|issn=0022-1767|pmc=PMC2936106|pmid=20498357}}</ref>For the first time (Lars Blom,Britta C. Poulsen,Bettina M. Jensen,Anker Hansen and Lars K. Poulsen published a journal online in 2011 Jul 6),indicating that TGF-β may be important for production of IL-9 but it is not only the definite requirement for IL-9 induction, since [[Cell culture|cultures]] with IL-33 without TGF-β have noticeably increased secretion of IL-9, suggesting an important role of IL-33, even though that the effect was not found significant on the [[gene]] level.<ref>{{Cite journal|last=Blom|first=Lars|last2=Poulsen|first2=Britta C.|last3=Jensen|first3=Bettina M.|last4=Hansen|first4=Anker|last5=Poulsen|first5=Lars K.|date=2011-07-06|title=IL-33 Induces IL-9 Production in Human CD4+ T Cells and Basophils|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130774/|journal=PLoS ONE|volume=6|issue=7|doi=10.1371/journal.pone.0021695|issn=1932-6203|pmc=PMC3130774|pmid=21765905}}</ref> 
== Gene location ==
The human IL-9 gene is located on the long arm of human [[Chromosome 5 (human)|chromosome 5]] at band 5q31-32, a region which is not found in a number of patients with acquired [[chromosome 5q deletion syndrome]].<ref name="pmid1901233">{{cite journal | vauthors = Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC | title = Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells | journal = Blood | volume = 77 | issue = 7 | pages = 1436–41 | year = 1991 | pmid = 1901233 | doi = 10.1182/blood.V77.7.1436.1436| url = http://www.bloodjournal.org/content/bloodjournal/77/7/1436.full.pdf | doi-access = free }}</ref>

== Protein structure ==
Human IL-9 [[protein]] sequence contains 144 residues with a typical [[signal peptide]] of 18 [[amino acid]]s. There is also the presence of 9 [[cysteine]]s in mature [[polypeptide]] and 4 [[N-linked glycosylation]] sites.<ref name="Renauld 1995 287–303"/> Until recently, IL-9 was thought to be evolutionary related to IL-7.<ref>{{cite journal|last1=Boulay|first1=J. L.|last2=Paul|first2=W. E.|date=1993-09-01|title=Hematopoietin sub-family classification based on size, gene organization and sequence homology|journal=Current Biology|volume=3|issue=9|pages=573–581|issn=0960-9822|pmid=15335670|doi=10.1016/0960-9822(93)90002-6|bibcode=1993CBio....3..573B |s2cid=42479456}}</ref> However, we know now that IL-9 is closer to IL-2 and IL-15 than to IL-7,<ref>{{cite journal|last=Reche|first=Pedro A.|date=2019-02-01|title=The tertiary structure of γc cytokines dictates receptor sharing|journal=Cytokine|volume=116|pages=161–168|doi=10.1016/j.cyto.2019.01.007|issn=1096-0023|pmid=30716660|s2cid=73449371}}</ref> at both the tertiary and amino acid sequence levels.

⚫
== Production ==
⚫
[[Interleukin 33]] (IL-33) induces IL-9 expression and secretion in [[T cell]]s, which was confirmed by the results obtained in mice by using Human ''[[in vitro]]''<nowiki/> system.<ref>{{cite journal | vauthors = Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK | title = IL-33, a potent inducer of adaptive immunity to intestinal nematodes | journal = Journal of Immunology | volume = 180 | issue = 4 | pages = 2443–9 | date = February 2008 | pmid = 18250453 | doi=10.4049/jimmunol.180.4.2443| doi-access = free }}</ref> Whereas the report of others confirms that [[TGF-b|TGF-β]] is an essential factor for IL-9 induction.<ref>{{cite journal | vauthors = Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA | title = TGF-beta induces IL-9 production from human Th17 cells | journal = Journal of Immunology | volume = 185 | issue = 1 | pages = 46–54 | date = July 2010 | pmid = 20498357 | pmc = 2936106 | doi = 10.4049/jimmunol.1000356 }}</ref> For the first time (Lars Blom, Britta C. Poulsen, Bettina M. Jensen, Anker Hansen and Lars K. Poulsen published a journal online in 2011 Jul 6),indicating that TGF-β may be important for production of IL-9 but it is not only the definite requirement for IL-9 induction, since [[Cell culture|cultures]] with IL-33 without TGF-β have noticeably increased secretion of IL-9, suggesting an important role of IL-33, even though that the effect was not found significant on the [[gene]] level.<ref>{{cite journal | vauthors = Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK | title = IL-33 induces IL-9 production in human CD4+ T cells and basophils | journal = PLOS ONE | volume = 6 | issue = 7 | pages = e21695 | date = 2011-07-06 | pmid = 21765905 | pmc = 3130774 | doi = 10.1371/journal.pone.0021695 | bibcode = 2011PLoSO...621695B | doi-access = free }}</ref>

[[File:IL9R_HUMAN.png|thumb|Interleukin-9 receptor]]
[[File:IL_9_functions.large.jpg|thumb|IL-9 has different direct and indirect effects on multiple cell types that affect the development of immunity and inflammation.|245x245px]]

== IL-9 expression ==
The analysis of IL-9 expression in different types of [[tumours]] such as Large cell anaplastic lymphoma (LCAL) and [[Hodgkin's Disease|Hodgkin's Disease (HD)]] by [[Northern blot|Northern blot analysis]] and [[in situ hybridization]] has showed that IL-9 is not involved as an autocrine growth factor in the [[pathogenesis]] of most [[B-cell lymphomas|B and T-cell lymphomas]], but it may have a part in HD and LCAL autocrine growth.

The further investigation could be done to conclude another probability, that, the [[in vivo]] [[Gene expression|overexpression]] of IL-9 might show the unique [[symptom]]s related to [[eosinophilia]] which was recently reported for [[Interleukin 5]] positive cases of HD.<ref name="pmid1908723">{{cite journal | vauthors = Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J | title = Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma | journal = Blood | volume = 78 | issue = 5 | pages = 1311–7 | year = 1991 | pmid = 1908723 | doi = 10.1182/blood.V78.5.1311.1311| url = http://www.bloodjournal.org/content/78/5/1311 | doi-access = free }}</ref>

IL-9 was found to be the first physiological stimulus triggering ''[[BCL3]]'' expression in [[T cell]]s and [[mast cell]]s by the analysis done in mouse.<ref name="pmid10361130">{{cite journal | vauthors = Richard M, Louahed J, Demoulin JB, Renauld JC | title = Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction | journal = Blood | volume = 93 | issue = 12 | pages = 4318–27 | year = 1999 | pmid = 10361130 | doi = 10.1182/blood.V93.12.4318| url = http://www.bloodjournal.org/content/93/12/4318 }}</ref>


== References ==
== References ==
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== Further reading ==
== Further reading ==
{{Refbegin|33em}}
{{Refbegin|33em}}
* {{cite journal | vauthors = Renauld JC, Houssiau F, Louahed J, Vink A, Van Snick J, Uyttenhove C | title = Interleukin-9 | journal = Advances in Immunology | volume = 54 | issue = | pages = 79–97 | year = 1993 | pmid = 8379467 | doi = 10.1016/S0065-2776(08)60533-7 | isbn = 978-0-12-022454-8 | series = Advances in Immunology }}
* {{cite book | vauthors = Renauld JC, Houssiau F, Louahed J, Vink A, Van Snick J, Uyttenhove C | title = Advances in Immunology Volume 54 | chapter = Interleukin-9 | volume = 54 | pages = 79–97 | year = 1993 | pmid = 8379467 | doi = 10.1016/S0065-2776(08)60533-7 | isbn = 978-0-12-022454-8 }}
* {{cite journal | vauthors = Knoops L, Renauld JC | title = IL-9 and its receptor: from signal transduction to tumorigenesis | journal = Growth Factors | volume = 22 | issue = 4 | pages = 207–15 | date = December 2004 | pmid = 15621723 | doi = 10.1080/08977190410001720879 }}
* {{cite journal | vauthors = Knoops L, Renauld JC | title = IL-9 and its receptor: from signal transduction to tumorigenesis | journal = Growth Factors | volume = 22 | issue = 4 | pages = 207–15 | date = December 2004 | pmid = 15621723 | doi = 10.1080/08977190410001720879 | s2cid = 40523692 }}
* {{cite journal | vauthors = Modi WS, Pollock DD, Mock BA, Banner C, Renauld JC, Van Snick J | title = Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 57 | issue = 2-3 | pages = 114–6 | year = 1991 | pmid = 1680606 | doi = 10.1159/000133126 }}
* {{cite journal | vauthors = Modi WS, Pollock DD, Mock BA, Banner C, Renauld JC, Van Snick J | title = Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 57 | issue = 2–3 | pages = 114–6 | year = 1991 | pmid = 1680606 | doi = 10.1159/000133126 }}
* {{cite journal | vauthors = Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC | title = Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells | journal = Blood | volume = 77 | issue = 7 | pages = 1436–41 | date = April 1991 | pmid = 1901233 | doi = }}
* {{cite journal | vauthors = Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC | title = Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells | journal = Blood | volume = 77 | issue = 7 | pages = 1436–41 | date = April 1991 | pmid = 1901233 | doi = 10.1182/blood.V77.7.1436.1436| doi-access = free }}
* {{cite journal | vauthors = Holbrook ST, Ohls RK, Schibler KR, Yang YC, Christensen RD | title = Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors | journal = Blood | volume = 77 | issue = 10 | pages = 2129–34 | date = May 1991 | pmid = 1903074 | doi = }}
* {{cite journal | vauthors = Holbrook ST, Ohls RK, Schibler KR, Yang YC, Christensen RD | title = Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors | journal = Blood | volume = 77 | issue = 10 | pages = 2129–34 | date = May 1991 | pmid = 1903074 | doi = 10.1182/blood.V77.10.2129.2129| doi-access = free }}
* {{cite journal | vauthors = Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J | title = Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma | journal = Blood | volume = 78 | issue = 5 | pages = 1311–7 | date = September 1991 | pmid = 1908723 | doi = }}
* {{cite journal | vauthors = Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J | title = Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma | journal = Blood | volume = 78 | issue = 5 | pages = 1311–7 | date = September 1991 | pmid = 1908723 | doi = 10.1182/blood.V78.5.1311.1311| doi-access = free }}
* {{cite journal | vauthors = Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J | title = Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene | journal = Journal of Immunology | volume = 144 | issue = 11 | pages = 4235–41 | date = June 1990 | pmid = 1971295 | doi = }}
* {{cite journal | vauthors = Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J | title = Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene | journal = Journal of Immunology | volume = 144 | issue = 11 | pages = 4235–41 | date = June 1990 | doi = 10.4049/jimmunol.144.11.4235 | pmid = 1971295 | s2cid = 30151082 }}
* {{cite journal | vauthors = Renauld JC, Goethals A, Houssiau F, Van Roost E, Van Snick J | title = Cloning and expression of a cDNA for the human homolog of mouse T cell and mast cell growth factor P40 | journal = Cytokine | volume = 2 | issue = 1 | pages = 9–12 | date = January 1990 | pmid = 2129501 | doi = 10.1016/1043-4666(90)90037-T }}
* {{cite journal | vauthors = Renauld JC, Goethals A, Houssiau F, Van Roost E, Van Snick J | title = Cloning and expression of a cDNA for the human homolog of mouse T cell and mast cell growth factor P40 | journal = Cytokine | volume = 2 | issue = 1 | pages = 9–12 | date = January 1990 | pmid = 2129501 | doi = 10.1016/1043-4666(90)90037-T | hdl = 2078.1/11464 }}
* {{cite journal | vauthors = Yang YC, Ricciardi S, Ciarletta A, Calvetti J, Kelleher K, Clark SC | title = Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40 | journal = Blood | volume = 74 | issue = 6 | pages = 1880–4 | date = November 1989 | pmid = 2508790 | doi = }}
* {{cite journal | vauthors = Yang YC, Ricciardi S, Ciarletta A, Calvetti J, Kelleher K, Clark SC | title = Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40 | journal = Blood | volume = 74 | issue = 6 | pages = 1880–4 | date = November 1989 | pmid = 2508790 | doi = 10.1182/blood.V74.6.1880.1880| doi-access = free }}
* {{cite journal | vauthors = Yin T, Keller SR, Quelle FW, Witthuhn BA, Tsang ML, Lienhard GE, Ihle JN, Yang YC | title = Interleukin-9 induces tyrosine phosphorylation of insulin receptor substrate-1 via JAK tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 270 | issue = 35 | pages = 20497–502 | date = September 1995 | pmid = 7544789 | doi = 10.1074/jbc.270.35.20497 }}
* {{cite journal | vauthors = Yin T, Keller SR, Quelle FW, Witthuhn BA, Tsang ML, Lienhard GE, Ihle JN, Yang YC | title = Interleukin-9 induces tyrosine phosphorylation of insulin receptor substrate-1 via JAK tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 270 | issue = 35 | pages = 20497–502 | date = September 1995 | pmid = 7544789 | doi = 10.1074/jbc.270.35.20497 | doi-access = free }}
* {{cite journal | vauthors = Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, Meyers DA, Levitt RC | title = Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy | journal = The New England Journal of Medicine | volume = 333 | issue = 14 | pages = 894–900 | date = October 1995 | pmid = 7666875 | doi = 10.1056/NEJM199510053331402 }}
* {{cite journal | vauthors = Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, Meyers DA, Levitt RC | title = Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy | journal = The New England Journal of Medicine | volume = 333 | issue = 14 | pages = 894–900 | date = October 1995 | pmid = 7666875 | doi = 10.1056/NEJM199510053331402 | doi-access =free }}
* {{cite journal | vauthors = Le Beau MM, Espinosa R, Neuman WL, Stock W, Roulston D, Larson RA, Keinanen M, Westbrook CA | title = Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 12 | pages = 5484–8 | date = June 1993 | pmid = 8516290 | pmc = 46745 | doi = 10.1073/pnas.90.12.5484 }}
* {{cite journal | vauthors = Le Beau MM, Espinosa R, Neuman WL, Stock W, Roulston D, Larson RA, Keinanen M, Westbrook CA | title = Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 12 | pages = 5484–8 | date = June 1993 | pmid = 8516290 | pmc = 46745 | doi = 10.1073/pnas.90.12.5484 | bibcode = 1993PNAS...90.5484B | doi-access = free }}
* {{cite journal | vauthors = Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld JC | title = A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9 | journal = Molecular and Cellular Biology | volume = 16 | issue = 9 | pages = 4710–6 | date = September 1996 | pmid = 8756628 | pmc = 231471 | doi = }}
* {{cite journal | vauthors = Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld JC | title = A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9 | journal = Molecular and Cellular Biology | volume = 16 | issue = 9 | pages = 4710–6 | date = September 1996 | pmid = 8756628 | pmc = 231471 | doi = 10.1128/mcb.16.9.4710}}
* {{cite journal | vauthors = Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC | title = Interleukin 9: a candidate gene for asthma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 24 | pages = 13175–80 | date = November 1997 | pmid = 9371819 | pmc = 24282 | doi = 10.1073/pnas.94.24.13175 }}
* {{cite journal | vauthors = Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC | title = Interleukin 9: a candidate gene for asthma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 24 | pages = 13175–80 | date = November 1997 | pmid = 9371819 | pmc = 24282 | doi = 10.1073/pnas.94.24.13175 | bibcode = 1997PNAS...9413175N | doi-access = free }}
* {{cite journal | vauthors = Demoulin JB, Van Roost E, Stevens M, Groner B, Renauld JC | title = Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 36 | pages = 25855–61 | date = September 1999 | pmid = 10464327 | doi = 10.1074/jbc.274.36.25855 }}
* {{cite journal | vauthors = Demoulin JB, Van Roost E, Stevens M, Groner B, Renauld JC | title = Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 36 | pages = 25855–61 | date = September 1999 | pmid = 10464327 | doi = 10.1074/jbc.274.36.25855 | doi-access = free}}
* {{cite journal | vauthors = Lejeune D, Demoulin JB, Renauld JC | title = Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling | journal = The Biochemical Journal | volume = 353 | issue = Pt 1 | pages = 109–116 | date = January 2001 | pmid = 11115404 | pmc = 1221548 | doi = 10.1042/0264-6021:3530109 }}
* {{cite journal | vauthors = Lejeune D, Demoulin JB, Renauld JC | title = Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling | journal = The Biochemical Journal | volume = 353 | issue = Pt 1 | pages = 109–116 | date = January 2001 | pmid = 11115404 | pmc = 1221548 | doi = 10.1042/0264-6021:3530109 }}
* {{cite journal | vauthors = Little FF, Cruikshank WW, Center DM | title = Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 25 | issue = 3 | pages = 347–52 | date = September 2001 | pmid = 11588013 | doi = 10.1165/ajrcmb.25.3.4349 }}
* {{cite journal | vauthors = Little FF, Cruikshank WW, Center DM | title = Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 25 | issue = 3 | pages = 347–52 | date = September 2001 | pmid = 11588013 | doi = 10.1165/ajrcmb.25.3.4349 }}
* {{cite journal | vauthors = Toda M, Tulic MK, Levitt RC, Hamid Q | title = A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma | journal = The Journal of Allergy and Clinical Immunology | volume = 109 | issue = 2 | pages = 246–50 | date = February 2002 | pmid = 11842292 | doi = 10.1067/mai.2002.121555 }}
* {{cite journal | vauthors = Toda M, Tulic MK, Levitt RC, Hamid Q | title = A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma | journal = The Journal of Allergy and Clinical Immunology | volume = 109 | issue = 2 | pages = 246–50 | date = February 2002 | pmid = 11842292 | doi = 10.1067/mai.2002.121555 | doi-access = free }}
* {{cite journal | vauthors = Pilette C, Ouadrhiri Y, Van Snick J, Renauld JC, Staquet P, Vaerman JP, Sibille Y | title = IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta | journal = Journal of Immunology | volume = 168 | issue = 8 | pages = 4103–11 | date = April 2002 | pmid = 11937570 | doi = 10.4049/jimmunol.168.8.4103 }}
* {{cite journal | vauthors = Pilette C, Ouadrhiri Y, Van Snick J, Renauld JC, Staquet P, Vaerman JP, Sibille Y | title = IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta | journal = Journal of Immunology | volume = 168 | issue = 8 | pages = 4103–11 | date = April 2002 | pmid = 11937570 | doi = 10.4049/jimmunol.168.8.4103 | doi-access = free }}
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[[Category:Interleukins]]
[[Category:Interleukins]]

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{{immunology-stub}}

Latest revision as of 11:27, 8 March 2024

IL9
Identifiers
AliasesIL9, HP40, IL-9, P40, interleukin 9
External IDsOMIM: 146931; MGI: 96563; HomoloGene: 492; GeneCards: IL9; OMA:IL9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3578

16198

Ensembl

ENSG00000145839

ENSMUSG00000021538

UniProt

P15248

P15247

RefSeq (mRNA)

NM_000590

NM_008373

RefSeq (protein)

NP_000581

NP_032399

Location (UCSC)Chr 5: 135.89 – 135.9 MbChr 13: 56.63 – 56.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interleukin 9, also known as IL-9, is a pleiotropic cytokine (cell signalling molecule) belonging to the group of interleukins.[5] IL-9 is produced by variety of cells like mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells in different amounts. Among them, Th9 cells are regarded as the major CD4+ T cells that produce IL-9.[6]

Functions[edit]

Il-9 is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells.[7] This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin-9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins namely STAT1, STAT3 and STAT5 and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness.[5]

Interleukin-9 has also shown to inhibit melanoma growth in mice. [8]

Additionally, it gives rise to the multiplication of hematologic neoplasias and also Hodgkin's lymphoma in humans but IL-9 also has antitumor properties in solid tumors, for example melanoma.[6]

Discovery[edit]

IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system.IL-9 remains an understudied cytokine even though it has been allocated with many biological functions. It was first purified and characterized as a T cell and mast cell growth factor and termed as P40, based on their molecular weight, or Mast cell growth-enhancing activity (MEA).The cloning and complete amino acid sequencing of P40 disclosed that it is structurally different from other T cells growth factors. So, it was named IL-9 based on its biological effects on both myeloid and lymphoid cells.[9]

The identification and cloning was first done by Yang and colleagues as a mitogenic factor for a human megakaryoblastic leukemia. The same human cDNA was isolated again by cross-hybridization with the mouse IL-9 probe.[10]

Gene location[edit]

The human IL-9 gene is located on the long arm of human chromosome 5 at band 5q31-32, a region which is not found in a number of patients with acquired chromosome 5q deletion syndrome.[11]

Protein structure[edit]

Human IL-9 protein sequence contains 144 residues with a typical signal peptide of 18 amino acids. There is also the presence of 9 cysteines in mature polypeptide and 4 N-linked glycosylation sites.[10] Until recently, IL-9 was thought to be evolutionary related to IL-7.[12] However, we know now that IL-9 is closer to IL-2 and IL-15 than to IL-7,[13] at both the tertiary and amino acid sequence levels.

Production[edit]

Interleukin 33 (IL-33) induces IL-9 expression and secretion in T cells, which was confirmed by the results obtained in mice by using Human in vitro system.[14] Whereas the report of others confirms that TGF-β is an essential factor for IL-9 induction.[15] For the first time (Lars Blom, Britta C. Poulsen, Bettina M. Jensen, Anker Hansen and Lars K. Poulsen published a journal online in 2011 Jul 6),indicating that TGF-β may be important for production of IL-9 but it is not only the definite requirement for IL-9 induction, since cultures with IL-33 without TGF-β have noticeably increased secretion of IL-9, suggesting an important role of IL-33, even though that the effect was not found significant on the gene level.[16]

Interleukin-9 receptor
IL-9 has different direct and indirect effects on multiple cell types that affect the development of immunity and inflammation.

IL-9 expression[edit]

The analysis of IL-9 expression in different types of tumours such as Large cell anaplastic lymphoma (LCAL) and Hodgkin's Disease (HD) by Northern blot analysis and in situ hybridization has showed that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B and T-cell lymphomas, but it may have a part in HD and LCAL autocrine growth.

The further investigation could be done to conclude another probability, that, the in vivo overexpression of IL-9 might show the unique symptoms related to eosinophilia which was recently reported for Interleukin 5 positive cases of HD.[17]

IL-9 was found to be the first physiological stimulus triggering BCL3 expression in T cells and mast cells by the analysis done in mouse.[18]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145839 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021538 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: IL9 interleukin 9".
  6. ^ a b Rojas-Zuleta WG, Sanchez E (2017). "IL-9: Function, Sources, and Detection". Th9 Cells. Methods in Molecular Biology. Vol. 1585. pp. 21–35. doi:10.1007/978-1-4939-6877-0_2. hdl:10161/14730. ISBN 978-1-4939-6876-3. PMID 28477184.
  7. ^ Perumal NB, Kaplan MH (2011). "Regulating IL9 transcription in T helper cells". Trends in Immunology. 32 (4): 146–50. doi:10.1016/j.it.2011.01.006. PMC 3070825. PMID 21371941.
  8. ^ Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS (August 2012). "Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells". Nature Medicine. 18 (8): 1248–53. doi:10.1038/nm.2856. PMC 3518666. PMID 22772464.
  9. ^ Goswami R, Kaplan MH (March 2011). "A brief history of IL-9". Journal of Immunology. 186 (6): 3283–8. doi:10.4049/jimmunol.1003049. PMC 3074408. PMID 21368237.
  10. ^ a b Renauld JC (1995). "Interleukin-9: Structural characteristics and biologic properties". Cytokines: Interleukins and Their Receptors. Cancer Treatment and Research. Vol. 80. Springer, Boston, MA. pp. 287–303. doi:10.1007/978-1-4613-1241-3_11. ISBN 9781461285281. PMID 8821582.
  11. ^ Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC (1991). "Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells" (PDF). Blood. 77 (7): 1436–41. doi:10.1182/blood.V77.7.1436.1436. PMID 1901233.
  12. ^ Boulay JL, Paul WE (1993-09-01). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–581. Bibcode:1993CBio....3..573B. doi:10.1016/0960-9822(93)90002-6. ISSN 0960-9822. PMID 15335670. S2CID 42479456.
  13. ^ Reche PA (2019-02-01). "The tertiary structure of γc cytokines dictates receptor sharing". Cytokine. 116: 161–168. doi:10.1016/j.cyto.2019.01.007. ISSN 1096-0023. PMID 30716660. S2CID 73449371.
  14. ^ Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK (February 2008). "IL-33, a potent inducer of adaptive immunity to intestinal nematodes". Journal of Immunology. 180 (4): 2443–9. doi:10.4049/jimmunol.180.4.2443. PMID 18250453.
  15. ^ Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA (July 2010). "TGF-beta induces IL-9 production from human Th17 cells". Journal of Immunology. 185 (1): 46–54. doi:10.4049/jimmunol.1000356. PMC 2936106. PMID 20498357.
  16. ^ Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK (2011-07-06). "IL-33 induces IL-9 production in human CD4+ T cells and basophils". PLOS ONE. 6 (7): e21695. Bibcode:2011PLoSO...621695B. doi:10.1371/journal.pone.0021695. PMC 3130774. PMID 21765905.
  17. ^ Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J (1991). "Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma". Blood. 78 (5): 1311–7. doi:10.1182/blood.V78.5.1311.1311. PMID 1908723.
  18. ^ Richard M, Louahed J, Demoulin JB, Renauld JC (1999). "Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction". Blood. 93 (12): 4318–27. doi:10.1182/blood.V93.12.4318. PMID 10361130.

Further reading[edit]

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