Interleukin 9

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AliasesIL9, HP40, IL-9, P40, interleukin 9
External IDsOMIM: 146931 MGI: 96563 HomoloGene: 492 GeneCards: IL9
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 5: 135.89 – 135.9 MbChr 13: 56.63 – 56.63 Mb
PubMed search[3][4]
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]


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]


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

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.


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

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]


  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/ 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 J (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, J. L.; Paul, W. E. (1993-09-01). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–581. doi:10.1016/0960-9822(93)90002-6. ISSN 0960-9822. PMID 15335670. S2CID 42479456.
  13. ^ Reche, Pedro A. (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. 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