IL-9 is a multifunctional cytokine, belong to a family of cytokines. IL-9 was initially reported as a T cell growth factor in mice. It is now known to target multiple cell types. It plays an important role in the expansion and recruitment of mast cells in response to intestinal nematode infection or during autoimmune encephalomyelitis (1,2). It is also known to act on various cell types known to be involved in asthma including T cells, B cells, mast cells, eosinophils, neutrophils, and epithelial cells (3). IL‑9 can promote the expression of TGF-beta in lipopolysaccharide induced monocytes and macrophages (4,5). IL-9 is also known to play important roles in conditions including airway inflammation (6,7,8), EAE (9,10,11,12,13) and parasitic infections (14,15,16). Mitogen-activated protein kinase pathway is activated transiently by IL-9, which in turn leads to the growth stimulation of hematopoietic cell lines (17). IL-9 signals through the heterodimeric receptor composed of a specific chain (IL-9R) and a gamma chain (IL2RG), which is shared between IL-2, IL-4, IL-7, IL15 and IL-21 (18). The IL-9R and IL-2RG associates with JAK1 and JAK3 respectively. Receptor engagement results in JAK1- JAK3 cross phosphorylation and activation of the JAK proteins which leads to the activation of Signal transducer and activator of transcription (STAT-1, STAT-3 and STAT-5) and Insulin receptor substrate 1 and 2 (IRS1 and IRS2)/PI3K cascades. IL-9 stimulation also results in the activation of MEK/ERK signaling cascade (19).

References

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4)Pilette C, Ouadrhiri Y, Van Snick J, Renauld JC, Staquet P, Vaerman JP, Sibille Y.IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta.J Immunol. 2002 ,168(8):4103-11. PMID:11937570

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6)Chang HC, Sehra S, Goswami R, Yao W, Yu Q, Stritesky GL, Jabeen R, McKinley C, Ahyi AN, Han L, Nguyen ET, Robertson MJ, Perumal NB, Tepper RS, Nutt SL, Kaplan MH.The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation.Nat Immunol. 2010;11(6):527-34. PMID: 20431622

7)Jones TG, Hallgren J, Humbles A, Burwell T, Finkelman FD, Alcaide P, Austen KF, Gurish MF.Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells.J Immunol. 2009 ;183(8):5251-60.PMID: 19783672

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10)Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, Bettelli E, Oukka M, van Snick J, Renauld JC, Kuchroo VK, Khoury SJ.IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells.Proc Natl Acad Sci U S A. 2009 ;106(31):12885-90PMID: 19433802

11)Li H, Nourbakhsh B, Ciric B, Zhang GX, Rostami A.Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by decreasing the effector T cell population.J Immunol. 2010 ;185(7):4095-100.PMID: 20805418

12)Jäger A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK.Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes.J Immunol. 2009 ;183(11):7169-77 PMID: 19890056

13)Peron JP, Yang K, Chen ML, Brandao WN, Basso AS, Commodaro AG, Weiner HL, Rizzo LV.Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice.J Neuroimmunol. 2010 ;227(1-2):10-7.PMID: 20580440

14)Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH, McKenzie NA.IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development.Immunity. 2000 ;13(4):573-83.PMID: 11070175

15)Khan WI, Richard M, Akiho H, Blennerhasset PA, Humphreys NE, Grencis RK, Van Snick J, Collins SM.Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections.Infect Immun. 2003;71(5):2430-8.PMID: 12704113

16)Richard M, Grencis RK, Humphreys NE, Renauld JC, Van Snick J.Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice.Proc Natl Acad Sci U S A. 2000 ;97(2):767-72.PMID: 10639154.

17) Demoulin JB, Louahed J, Dumoutier L, Stevens M, Renauld JC. MAP kinase activation by interleukin-9 in lymphoid and mast cell lines. Oncogene. 2003 Mar 27;22(12):1763-70. PMID: 12660812.

18)Demoulin JB, Renauld JC.Interleukin 9 and its receptor: an overview of structure and function.Int Rev Immunol. 1998;16(3-4):345-64.PMID: 9505195

19)Knoops L, Renauld JC. IL-9 and its receptor: from signal transduction to tumorigenesis. Growth Factors. 2004 Dec;22(4):207-15. Review. PMID:15621723.