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]
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 receptorIL-9 has different direct and indirect effects on multiple cell types that affect the development of immunity and inflammation.
The further investigation could be done to conclude another probability, that, the in vivooverexpression 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]
^ abRenauld 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. ISBN9781461285281. PMID8821582.
Modi WS, Pollock DD, Mock BA, Banner C, Renauld JC, Van Snick J (1991). "Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization". Cytogenetics and Cell Genetics. 57 (2–3): 114–6. doi:10.1159/000133126. PMID1680606.
Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (June 1990). "Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene". Journal of Immunology. 144 (11): 4235–41. doi:10.4049/jimmunol.144.11.4235. PMID1971295. S2CID30151082.
Renauld JC, Goethals A, Houssiau F, Van Roost E, Van Snick J (January 1990). "Cloning and expression of a cDNA for the human homolog of mouse T cell and mast cell growth factor P40". Cytokine. 2 (1): 9–12. doi:10.1016/1043-4666(90)90037-T. hdl:2078.1/11464. PMID2129501.
Little FF, Cruikshank WW, Center DM (September 2001). "Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells". American Journal of Respiratory Cell and Molecular Biology. 25 (3): 347–52. doi:10.1165/ajrcmb.25.3.4349. PMID11588013.
