Interleukin-9

Interleukin 9, also known as IL-9, is a pleiotropic cytokine (cell signalling molecule) belonging to the group of interleukins. 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.

Functions

Il-9 is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells. 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.

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

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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.

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 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.

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.

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.

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. Until recently, IL-9 was thought to be evolutionary related to IL-7. However, we know now that IL-9 is closer to IL-2 and IL-15 than to IL-7, 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. Whereas the report of others confirms that TGF-β is an essential factor for IL-9 induction. 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.

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.

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.

References

Further reading

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{{Interleukin receptor modulators

Interleukins