Interleukin 9

Last updated

IL9
Identifiers
Aliases IL9 , HP40, IL-9, P40, interleukin 9
External IDs OMIM: 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 Mb Chr 13: 56.63 – 56.63 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

Functions

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 been 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

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 despite the attribution of many biological functions to it. IL-9 was first purified and characterized as a T cell and mast cell growth factor and termed as P40, based on its molecular weight, or MEA, based on its mast cell growth-enhancing activity. The cloning and complete amino acid sequencing of P40 disclosed that it is structurally different from other T cell growth factors. It was therefore 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

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

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

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 IL9R HUMAN.png
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 functions.large.jpg
IL-9 has different direct and indirect effects on multiple cell types that affect the development of immunity and inflammation.

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 (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]

Related Research Articles

<span class="mw-page-title-main">Cytokine</span> Broad and loose category of small proteins important in cell signaling

Cytokines (/'saɪ.tə.kaɪn/) are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

<span class="mw-page-title-main">Eosinophil</span> Variety of white blood cells

Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.

Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.

<span class="mw-page-title-main">FOXP3</span> Immune response protein

FOXP3, also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues.

<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

<span class="mw-page-title-main">Interleukin 5</span> Type of cytokine

Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells.

<span class="mw-page-title-main">TGF beta 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.

<span class="mw-page-title-main">Interleukin 23 subunit alpha</span>

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. The protein is also known as IL-23p19. It is one of the two subunits of the cytokine Interleukin-23.

<span class="mw-page-title-main">Interleukin 11</span> Protein-coding gene in the species Homo sapiens

Interleukin 11 is a protein that in humans is encoded by the IL11 gene.

<span class="mw-page-title-main">Interleukin 21</span> Mammalian protein found in humans

Interleukin 21 (IL-21) is a protein that in humans is encoded by the IL21 gene.

<span class="mw-page-title-main">Interleukin 30</span> Protein-coding gene in the species Homo sapiens

Interleukin 30 (IL-30) forms one chain of the heterodimeric cytokine called interleukin 27 (IL-27), thus it is also called IL27-p28. IL-27 is composed of α chain p28 and β chain Epstain-Barr induce gene-3 (EBI3). The p28 subunit, or IL-30, has an important role as a part of IL-27, but it can be secreted as a separate monomer and has its own functions in the absence of EBI3. The discovery of IL-30 as individual cytokine is relatively new and thus its role in the modulation of the immune response is not fully understood.

<span class="mw-page-title-main">Interleukin 22</span> Protein, encoded in humans by IL22 gene

Interleukin-22 (IL-22) is a protein that in humans is encoded by the IL22 gene.

<span class="mw-page-title-main">Interleukin 19</span> Protein-coding gene in the species Homo sapiens

Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.

Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.

<span class="mw-page-title-main">Interleukin-12 subunit beta</span> Protein-coding gene in the species Homo sapiens

Subunit beta of interleukin 12 is a protein subunit that in humans is encoded by the IL12B gene. IL-12B is a common subunit of interleukin 12 and interleukin 23.

Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.

<span class="mw-page-title-main">Interleukin-9 receptor</span> Protein-coding gene in the species Homo sapiens

Interleukin 9 receptor (IL9R) also known as CD129 is a type I cytokine receptor. IL9R also denotes its human gene.

<span class="mw-page-title-main">Interleukin 20 receptor, beta subunit</span> Protein-coding gene in the species Homo sapiens

Interleukin 20 receptor, beta subunit is a subunit of the interleukin-20 receptor and interleukin-22 receptor. It is believed to be involved in both pro-inflammatory and anti-inflammatory responses.

<span class="mw-page-title-main">IL2RA</span> Mammalian protein found in Homo sapiens

The interleukin-2 receptor alpha chain is a protein involved in the assembly of the high-affinity interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.

In cell biology, TH9 cells are a sub-population of CD4+T cells that produce interleukin-9 (IL-9). They play a role in defense against helminth infections, in allergic responses, in autoimmunity, and tumor suppression.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000145839 – Ensembl, May 2017
  2. 1 2 3 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. 1 2 "Entrez Gene: IL9 interleukin 9".
  6. 1 2 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. 1 2 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.

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