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Gene Review

Il9  -  interleukin 9

Mus musculus

Synonyms: Cytokine P40, IL-9, Il-9, Interleukin-9, P40, ...
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Disease relevance of Il9

  • We have used mice genetically deficient in IL-9 to determine the role of this cytokine in the pathophysiologic features of the allergic pulmonary response-airway hyperreactivity (AHR) and eosinophilia [1].
  • Goblet cell hyperplasia and immunoglobulin (Ig) E production were also unaffected by the lack of IL-9 [1].
  • The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity [1].
  • Interleukin-9 is a major anti-apoptotic factor for thymic lymphomas [2].
  • In this study we demonstrate that IL-9 is expressed early during the Th2-type response and that its elevation in vivo results in the enhancement of intestinal mastocytosis and the production of both the immunoglobulin E (IgE) and IgG1 isotypes [3].

High impact information on Il9


Chemical compound and disease context of Il9

  • In this study, an antimouse IL-9 (anti-mIL-9) antibody (Ab) was evaluated against pulmonary eosinophilia, histopathologic changes in lung tissues, serum immunoglobulin (Ig) E levels, and airway hyperresponsiveness (AHR) to methacholine in mice sensitized and challenged with ovalbumin (OVA) [8].
  • Intracerebral injection of the glutamatergic analogue ibotenate to newborn mice induces cortical plate and white matter lesions mimicking the brain damage associated with cerebral palsy, and pretreatment with proinflammatory cytokines such as interleukin-1-beta or with interleukin-9 significantly exacerbates these lesions [9].
  • Histamine and IL-9 are suspected to play an important role in the pathogenesis of asthmatic and allergic reactions [10].

Biological context of Il9


Anatomical context of Il9


Associations of Il9 with chemical compounds

  • We have demonstrated that IL-9 is not required for the development of a robust Th2 response to allergen in sensitized mice [1].
  • Moreover, IL-4 and IL-9 maintained proliferation of these cells in the presence of DEX [2].
  • Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9 [14].
  • However, IL-9 acted synergistically with IL-7 and PHA to stimulate the proliferation of irradiated cells during the second post-irradiation phase [17].
  • In addition, IL-9, -13, and -15 were significantly elevated only following toluene diisocyanate exposure [18].

Physical interactions of Il9


Regulatory relationships of Il9


Other interactions of Il9

  • A significant inverse correlation between lung Ugrp1 mRNA levels and IL-9 levels in BAL fluid was demonstrated by regression analysis (r = 0.616, P = 0.023) [24].
  • However, IL-3 increased GTP binding to M-Ras, suggesting that M-Ras induction might represent a new mechanism of cooperativity between cytokines such as IL-3 and IL-9 [11].
  • In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor [14].
  • This observation led us to investigate the functional link between IL-9 and IL-5 production during alloreactive T cell responses in vitro and in vivo [20].
  • To characterize the specificity of IL-9-mediated T cell activation, we used a murine T cell clone that could grow with either IL-9 or IL-2 [13].

Analytical, diagnostic and therapeutic context of Il9


  1. The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. McMillan, S.J., Bishop, B., Townsend, M.J., McKenzie, A.N., Lloyd, C.M. J. Exp. Med. (2002) [Pubmed]
  2. Interleukin-9 is a major anti-apoptotic factor for thymic lymphomas. Renauld, J.C., Vink, A., Louahed, J., Van Snick, J. Blood (1995) [Pubmed]
  3. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Faulkner, H., Renauld, J.C., Van Snick, J., Grencis, R.K. Infect. Immun. (1998) [Pubmed]
  4. IL-15 and IL-2: a matter of life and death for T cells in vivo. Li, X.C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T.R., Strom, T.B. Nat. Med. (2001) [Pubmed]
  5. Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Mehler, M.F., Rozental, R., Dougherty, M., Spray, D.C., Kessler, J.A. Nature (1993) [Pubmed]
  6. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Fallon, P.G., Jolin, H.E., Smith, P., Emson, C.L., Townsend, M.J., Fallon, R., Smith, P., McKenzie, A.N. Immunity (2002) [Pubmed]
  7. IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Townsend, J.M., Fallon, G.P., Matthews, J.D., Smith, P., Jolin, E.H., McKenzie, N.A. Immunity (2000) [Pubmed]
  8. Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice. Kung, T.T., Luo, B., Crawley, Y., Garlisi, C.G., Devito, K., Minnicozzi, M., Egan, R.W., Kreutner, W., Chapman, R.W. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  9. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. Mesples, B., Plaisant, F., Gressens, P. Brain Res. Dev. Brain Res. (2003) [Pubmed]
  10. IL-9 increases the expression of several cytokines in activated mast cells, while the IL-9-induced IL-9 production is inhibited in mast cells of histamine-free transgenic mice. Wiener, Z., Falus, A., Toth, S. Cytokine (2004) [Pubmed]
  11. Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones. Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N.C., Levitt, R.C., Renauld, J.C. Blood (1999) [Pubmed]
  12. Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction. Richard, M., Louahed, J., Demoulin, J.B., Renauld, J.C. Blood (1999) [Pubmed]
  13. IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. Louahed, J., Kermouni, A., Van Snick, J., Renauld, J.C. J. Immunol. (1995) [Pubmed]
  14. JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. Yin, T., Tsang, M.L., Yang, Y.C. J. Biol. Chem. (1994) [Pubmed]
  15. Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9 transgenic mice. Lange, K., Uckert, W., Blankenstein, T., Nadrowitz, R., Bittner, C., Renauld, J.C., van Snick, J., Feller, A.C., Merz, H. Oncogene (2003) [Pubmed]
  16. Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population. Vink, A., Warnier, G., Brombacher, F., Renauld, J.C. J. Exp. Med. (1999) [Pubmed]
  17. Elevated interleukin-9 receptor expression and response to interleukins-9 and -7 in thymocytes during radiation-induced T-cell lymphomagenesis in B6C3F1 mice. Nishimura, M., Kakinuma, S., Yamamoto, D., Kobayashi, Y., Suzuki, G., Sado, T., Shimada, Y. J. Cell. Physiol. (2004) [Pubmed]
  18. The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, dinitrofluorobenzene, and toluene diisocyanate exposure. Manetz, T.S., Pettit, D.A., Meade, B.J. Toxicol. Appl. Pharmacol. (2001) [Pubmed]
  19. Interleukin-9 promotes eosinophilic rejection of mouse heart allografts. Poulin, L.F., Richard, M., Le Moine, A., Kiss, R., McKenzie, A.N., Goldman, M., Renauld, J.C., Van Snick, J., Braun, M.Y. Transplantation (2003) [Pubmed]
  20. Interleukin-9 stimulates the production of interleukin-5 in CD4+ T cells. Poulin, L.F., Habran, C., Stordeur, P., Goldman, M., McKenzie, A., Van Snick, J., Renauld, J.C., Braun, M.Y. Eur. Cytokine Netw. (2005) [Pubmed]
  21. Distinct actions of interleukin-9 and interleukin-4 on a hematopoietic stem cell line, EMLC1. Wang, X.Y., Gelfanov, V., Sun, H.B., Tsai, S., Yang, Y.C. Exp. Hematol. (1999) [Pubmed]
  22. Murine bone marrow-derived mast cells as potent producers of IL-9: costimulatory function of IL-10 and kit ligand in the presence of IL-1. Stassen, M., Arnold, M., Hültner, L., Müller, C., Neudörfl, C., Reineke, T., Schmitt, E. J. Immunol. (2000) [Pubmed]
  23. IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. Steenwinckel, V., Louahed, J., Orabona, C., Huaux, F., Warnier, G., McKenzie, A., Lison, D., Levitt, R., Renauld, J.C. J. Immunol. (2007) [Pubmed]
  24. Decreased expression of uteroglobin-related protein 1 in inflamed mouse airways is mediated by IL-9. Chiba, Y., Kusakabe, T., Kimura, S. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  25. Induction of enhanced immunity to intestinal nematodes using IL-9-producing dendritic cells. Leech, M.D., Grencis, R.K. J. Immunol. (2006) [Pubmed]
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