interleukin 9

Summary

Summary: A multifunctional cytokine secreted by primarily by activated TH2 CELLS that may play a role as a regulator of allergic INFLAMMATION. It has been shown to enhance the growth and CELL DIFFERENTIATION of MAST CELLS, and can act on a variety of other immune cells.

Top Publications

  1. Fallon P, Jolin H, Smith P, Emson C, Townsend M, Fallon R, et al. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity. 2002;17:7-17 pubmed
    ..These mice reveal distinct spatial, temporal, and hierarchical cytokine requirements in immune function...
  2. Soussi Gounni A, Kontolemos M, Hamid Q. Role of IL-9 in the pathophysiology of allergic diseases. J Allergy Clin Immunol. 2001;107:575-82 pubmed
    ..IL-9 has been shown to act on many cell types involved in asthma, including T cells, B cells, mast cells, eosinophils, neutrophils, and epithelial cells, and thus might be important in the pathophysiology of allergic asthma. ..
  3. Louahed J, Zhou Y, Maloy W, Rani P, Weiss C, Tomer Y, et al. Interleukin 9 promotes influx and local maturation of eosinophils. Blood. 2001;97:1035-42 pubmed
    The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known...
  4. Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel R, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol. 2008;9:1347-55 pubmed publisher
    ..Thus IL-9(+)IL-10(+) T cells lack suppressive function and constitute a distinct population of helper-effector T cells that promote tissue inflammation. ..
  5. Arendse B, Van Snick J, Brombacher F. IL-9 is a susceptibility factor in Leishmania major infection by promoting detrimental Th2/type 2 responses. J Immunol. 2005;174:2205-11 pubmed
    ..The results extend efforts made to generate autoantibodies capable of regulating biological processes, with IL-9 a potential drug target against leishmaniasis. ..
  6. Cheng G, Arima M, Honda K, Hirata H, Eda F, Yoshida N, et al. Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model. Am J Respir Crit Care Med. 2002;166:409-16 pubmed
    ..Taken together, our findings emphasize the importance of IL-9 in the pathogenesis of asthma and suggest that blockade of IL-9 may be a new therapeutic strategy for bronchial asthma. ..
  7. Van Snick J, Goethals A, Renauld J, Van Roost E, Uyttenhove C, Rubira M, et al. Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J Exp Med. 1989;169:363-8 pubmed
    ..Here, we report the cloning and expression of a cDNA for this new growth factor. The predicted mature protein is a cationic cysteine-rich polypeptide of 14 kD without significant homology to previously sequenced proteins. ..
  8. Patkai J, Mesples B, Dommergues M, Fromont G, Thornton E, Renauld J, et al. Deleterious effects of IL-9-activated mast cells and neuroprotection by antihistamine drugs in the developing mouse brain. Pediatr Res. 2001;50:222-30 pubmed
    ..Neuroprotective strategies targeting mast cells may be useful in some neonates at risk for cerebral palsy. ..
  9. Townsend J, Fallon G, Matthews J, Smith P, Jolin E, McKenzie N. IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity. 2000;13:573-83 pubmed
    ..Thus, deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation...

More Information

Publications62

  1. Kung T, Luo B, Crawley Y, Garlisi C, DeVito K, Minnicozzi M, et al. Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice. Am J Respir Cell Mol Biol. 2001;25:600-5 pubmed
    ..A single dose of the antibody was ineffective on all measures. These results indicate that an antibody to mIL-9 inhibits the development of allergic pulmonary inflammation and AHR in mice. ..
  2. Ying S, Meng Q, Kay A, Robinson D. Elevated expression of interleukin-9 mRNA in the bronchial mucosa of atopic asthmatics and allergen-induced cutaneous late-phase reaction: relationships to eosinophils, mast cells and T lymphocytes. Clin Exp Allergy. 2002;32:866-71 pubmed
    ..707, P = 0.015). Elevated expression of IL-9 in allergic inflammation may contribute to local eosinophil infiltration and survival in asthma and other allergic atopic diseases. ..
  3. Baraldo S, Faffe D, Moore P, Whitehead T, McKenna M, Silverman E, et al. Interleukin-9 influences chemokine release in airway smooth muscle: role of ERK. Am J Physiol Lung Cell Mol Physiol. 2003;284:L1093-102 pubmed
    ..Our results indicate that airway smooth muscle is a target for IL-9 and that IL-9 amplifies the potential for these cells to recruit eosinophils and neutrophils into the airways by a mechanism involving ERK. ..
  4. Matsuzawa S, Sakashita K, Kinoshita T, Ito S, Yamashita T, Koike K. IL-9 enhances the growth of human mast cell progenitors under stimulation with stem cell factor. J Immunol. 2003;170:3461-7 pubmed
    ..Taken together, IL-9 appears to act as a potent enhancer for the SCF-dependent growth of mast cell progenitors in humans, particularly asthmatic patients. ..
  5. Erpenbeck V, Hohlfeld J, Volkmann B, Hagenberg A, Geldmacher H, Braun A, et al. Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes. J Allergy Clin Immunol. 2003;111:1319-27 pubmed
    ..Lymphocytes are the major cellular source of IL-9. The increased expression and its correlation with eosinophil numbers suggest a potential role for IL-9 in the late phase of the allergic response. ..
  6. Forbes E, Groschwitz K, Abonia J, Brandt E, Cohen E, Blanchard C, et al. IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med. 2008;205:897-913 pubmed publisher
    ..These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9-mediated mast cell responses have an important role in food allergy. ..
  7. Elyaman W, Bradshaw E, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci U S A. 2009;106:12885-90 pubmed publisher
    ..The mechanism of IL-9 effects on T(H)17 and T(regs) is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses. ..
  8. Demoulin J, Louahed J, Dumoutier L, Stevens M, Renauld J. MAP kinase activation by interleukin-9 in lymphoid and mast cell lines. Oncogene. 2003;22:1763-70 pubmed
    ..In summary, these results indicate that IL-9 can transiently activate the mitogen-activated protein kinase pathway, which contributes to growth stimulation of hematopoietic cell lines. ..
  9. Reader J, Hyde D, Schelegle E, Aldrich M, Stoddard A, McLane M, et al. Interleukin-9 induces mucous cell metaplasia independent of inflammation. Am J Respir Cell Mol Biol. 2003;28:664-72 pubmed
    ..IL-9 seems to directly stimulate mucous cell metaplasia without the requirement of inflammatory cell influx. ..
  10. McDermott J, Bartram R, Knight P, Miller H, Garrod D, Grencis R. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci U S A. 2003;100:7761-6 pubmed
    ..These results provide the mechanism whereby mucosal mast cells mediate parasite expulsion from the intestine. ..
  11. Ikeda R, Miller M, Nayar J, Walker L, Cho J, McElwain K, et al. Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: modulation by immunostimulatory DNA sequences. J Immunol. 2003;171:4860-7 pubmed
  12. Glimelius I, Edström A, Amini R, Fischer M, Nilsson G, Sundstrom C, et al. IL-9 expression contributes to the cellular composition in Hodgkin lymphoma. Eur J Haematol. 2006;76:278-83 pubmed
    ..IL-9 expression is related to the histology, clinical picture and the presence of eosinophils and mast cells in HL. These results indicate that IL-9 is an important part of the cytokine network and inflammatory infiltrate in HL. ..
  13. Temann U, Ray P, Flavell R. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J Clin Invest. 2002;109:29-39 pubmed
    ..These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully. ..
  14. Steenwinckel V, Louahed J, Lemaire M, Sommereyns C, Warnier G, McKenzie A, et al. IL-9 promotes IL-13-dependent paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa. J Immunol. 2009;182:4737-43 pubmed publisher
    ..Taken together, our data indicate that Paneth cell hyperplasia and expression of their various antimicrobial products contribute to the immune response driven by TH2 cytokines, such as IL-9 and IL-13 in the intestinal mucosa...
  15. Merz H, Houssiau F, Orscheschek K, Renauld J, Fliedner A, Herin M, et al. Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma. Blood. 1991;78:1311-7 pubmed
    ..These results suggest that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B- and T-cell lymphomas, but that it may play a role in HD and LCAL. ..
  16. Jones T, Hallgren J, Humbles A, Burwell T, Finkelman F, Alcaide P, et al. Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol. 2009;183:5251-60 pubmed publisher
    ..These findings implicate type 2 NKT cells and IL-9 as central regulators that function in the same pathway mediating the Ag-induced increase in numbers of pulmonary MCp. ..
  17. Abdelilah S, Latifa K, Esra N, Cameron L, Bouchaib L, Nicolaides N, et al. Functional expression of IL-9 receptor by human neutrophils from asthmatic donors: role in IL-8 release. J Immunol. 2001;166:2768-74 pubmed
    ..Taken together, these findings suggest a novel role for PMNs in allergic disease through the expression and activation of the IL-9R. ..
  18. Uyttenhove C, Simpson R, Van Snick J. Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci U S A. 1988;85:6934-8 pubmed
    ..Of a number of cell lines, only helper T cells responded to P40, and this response was not mediated by either interleukin 2 or interleukin 4. ..
  19. Renauld J, van der Lugt N, Vink A, van Roon M, Godfraind C, Warnier G, et al. Thymic lymphomas in interleukin 9 transgenic mice. Oncogene. 1994;9:1327-32 pubmed
    Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo...
  20. Levitt R, McLane M, MacDonald D, Ferrante V, Weiss C, Zhou T, et al. IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders. J Allergy Clin Immunol. 1999;103:S485-91 pubmed
    ..These data support a central role for the IL-9 pathway in the complex pathogenesis of allergic inflammation. ..
  21. Demoulin J, Uyttenhove C, Lejeune D, Mui A, Groner B, Renauld J. STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells. Cancer Res. 2000;60:3971-7 pubmed
    ..Our data suggest that STAT5 is an important mediator of IL-9-driven proliferation and that dysregulation of STAT5 activation favors tumorigenesis of lymphoid cells. ..
  22. Demoulin J, Grasso L, Atkins J, Stevens M, Louahed J, Levitt R, et al. Role of insulin receptor substrate-2 in interleukin-9-dependent proliferation. FEBS Lett. 2000;482:200-4 pubmed
    ..Finally, 32D cells that were transfected with the IL-9 receptor but lack IRS expression survived in the presence of IL-9. Ectopic IRS1 expression allowed for IL-9-induced proliferation, in the absence of significant PKB phosphorylation. ..
  23. Nicolaides N, Holroyd K, Ewart S, Eleff S, Kiser M, Dragwa C, et al. Interleukin 9: a candidate gene for asthma. Proc Natl Acad Sci U S A. 1997;94:13175-80 pubmed
    ..We assessed bronchial responsiveness as a quantitative trait in mice and found it linked to chromosome 13. Interleukin 9 (IL-9) is located in the linked region and was analyzed as a gene candidate...
  24. Lu L, Lind E, Gondek D, Bennett K, Gleeson M, Pino Lagos K, et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 2006;442:997-1002 pubmed
    ..Finally, immunohistochemical analysis clearly demonstrates the existence of this novel T(Reg)-IL-9-mast cell relationship within tolerant allografts. ..
  25. Knoops L, Louahed J, Van Snick J, Renauld J. IL-9 promotes but is not necessary for systemic anaphylaxis. J Immunol. 2005;175:335-41 pubmed
    ..Taken together, the data reported in this study indicate that IL-9 promotes systemic anaphylaxis reactions, acting at both the sensitization and effector stages, but is not absolutely required for this process. ..
  26. Steenwinckel V, Louahed J, Orabona C, Huaux F, Warnier G, McKenzie A, et al. IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. J Immunol. 2007;178:3244-51 pubmed
  27. Veldhoen M, Uyttenhove C, Van Snick J, Helmby H, Westendorf A, Buer J, et al. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008;9:1341-6 pubmed publisher
    ..Thus, transforming growth factor-beta constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways. ..
  28. Hauber H, Bergeron C, Hamid Q. IL-9 in allergic inflammation. Int Arch Allergy Immunol. 2004;134:79-87 pubmed
    ..Furthermore, the specific role of IL-9 in allergic diseases and the potential therapeutic approach of blocking IL-9 will be discussed. ..
  29. McNamara P, Flanagan B, Baldwin L, Newland P, Hart C, Smyth R. Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis. Lancet. 2004;363:1031-7 pubmed
    ..b>Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma...
  30. Tsicopoulos A, Shimbara A, de Nadai P, Aldewachi O, Lamblin C, Lassalle P, et al. Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis. J Allergy Clin Immunol. 2004;113:462-9 pubmed
    ..These results suggest an important role for IL-9 in the pathogenesis of BHR and a causal relation between IL-9 and the development of bronchial eosinophilia in asthma. ..
  31. Godfraind C, Louahed J, Faulkner H, Vink A, Warnier G, Grencis R, et al. Intraepithelial infiltration by mast cells with both connective tissue-type and mucosal-type characteristics in gut, trachea, and kidneys of IL-9 transgenic mice. J Immunol. 1998;160:3989-96 pubmed
  32. Eklund K, Ghildyal N, Austen K, Stevens R. Induction by IL-9 and suppression by IL-3 and IL-4 of the levels of chromosome 14-derived transcripts that encode late-expressed mouse mast cell proteases. J Immunol. 1993;151:4266-73 pubmed
  33. Faulkner H, Renauld J, Van Snick J, Grencis R. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect Immun. 1998;66:3832-40 pubmed
    ..muris. ..
  34. Zhou Y, McLane M, Levitt R. Th2 cytokines and asthma. Interleukin-9 as a therapeutic target for asthma. Respir Res. 2001;2:80-4 pubmed
    ..We also discuss these results in comparison with the experiments supporting the involvement of other T H2 cytokines such as IL-4, IL-5 and IL-13. ..
  35. Demoulin J, Van Roost E, Stevens M, Groner B, Renauld J. Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9. J Biol Chem. 1999;274:25855-61 pubmed
    ..These results suggest that survival and cell growth are redundantly controlled by multiple STAT factors, whereas differentiation gene induction is more specifically correlated with individual STAT activation by IL-9. ..
  36. Hültner L, Kölsch S, Stassen M, Kaspers U, Kremer J, Mailhammer R, et al. In activated mast cells, IL-1 up-regulates the production of several Th2-related cytokines including IL-9. J Immunol. 2000;164:5556-63 pubmed
    ..These results are of particular importance in the light of recent reports that strongly support a central role of IL-9 in allergic lung inflammation and in host defense against worm infections. ..
  37. Stassen M, Muller C, Arnold M, Hültner L, Klein Hessling S, Neudörfl C, et al. IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide: NF-kappa B is decisively involved in the expression of IL-9. J Immunol. 2001;166:4391-8 pubmed
  38. Gounni A, Hamid Q, Rahman S, Hoeck J, Yang J, Shan L. IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells. J Immunol. 2004;173:2771-9 pubmed
    ..Taken together, these data provide new evidence demonstrating that IL-9-dependent activation of ASM cells contributes to eosinophilic inflammation observed in asthma. ..
  39. Louahed J, Kermouni A, Van Snick J, Renauld J. IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. J Immunol. 1995;154:5061-70 pubmed
    b>Interleukin 9 (IL-9) is a TH2 cytokine that has been shown to promote the antigen-independent growth of some mouse T helper clones...
  40. Holgate S, Church M, Howarth P, Morton E, Frew A, Djukanovic R. Genetic and environmental influences on airway inflammation in asthma. Int Arch Allergy Immunol. 1995;107:29-33 pubmed
    ..These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma. ..
  41. Gessner A, Blum H, Rollinghoff M. Differential regulation of IL-9-expression after infection with Leishmania major in susceptible and resistant mice. Immunobiology. 1993;189:419-35 pubmed
    ..Treatment of BALB/c mice with neutralizing anti-IL-4 mAb, a regimen known to lead to subsequent cure of infected BALB/c mice, suppressed late IL-9 synthesis. ..
  42. White B, Leon F, White W, Robbie G. Two first-in-human, open-label, phase I dose-escalation safety trials of MEDI-528, a monoclonal antibody against interleukin-9, in healthy adult volunteers. Clin Ther. 2009;31:728-40 pubmed publisher
    ..The findings support further investigation of MEDI-528 in multiple-dose trials in patients with asthma. ClinicalTrials.gov Identification numbers: NCT00192296 (intravenous study); NCT00116168 (subcutaneous study). ..
  43. Temann U, Laouar Y, Eynon E, Homer R, Flavell R. IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells. Int Immunol. 2007;19:1-10 pubmed
    ..Our results implicate the lung epithelium as a potentially important source of inflammatory cytokines in asthma. ..
  44. Wang T, Chen W, Huang Y, Shih N, Feng W, Tseng H, et al. The synergistic effects of the IL-9 gene and environmental exposures on asthmatic Taiwanese families as determined by the transmission/disequilibrium test. Int J Immunogenet. 2006;33:105-10 pubmed
  45. Lejeune D, Demoulin J, Renauld J. Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling. Biochem J. 2001;353:109-116 pubmed
    b>Interleukin 9 (IL-9) is a cytokine preferentially produced by T helper type 2 lymphocytes and active on various cell types such as T- and B-lymphocytes, mast cells and haemopoietic progenitors...
  46. Renauld J, Houssiau F, Louahed J, Vink A, Van Snick J, Uyttenhove C. Interleukin-9. Adv Immunol. 1993;54:79-97 pubmed
  47. Knoops L, Renauld J. IL-9 and its receptor: from signal transduction to tumorigenesis. Growth Factors. 2004;22:207-15 pubmed
    ..Moreover, in vitro, dysregulated IL-9 response can lead to autonomous cell growth and malignant transformation of lymphoid cells associated with constitutive activation of the Jak/STAT pathway. ..
  48. Fallon P, Smith P, Richardson E, Jones F, Faulkner H, Van Snick J, et al. Expression of interleukin-9 leads to Th2 cytokine-dominated responses and fatal enteropathy in mice with chronic Schistosoma mansoni infections. Infect Immun. 2000;68:6005-11 pubmed
    ..This study highlights the pleiotropic in vivo activity of IL-9 and demonstrates that an elevated Th2 cytokine phenotype leads to death during murine schistosome infection. ..
  49. Demoulin J, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, et al. A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9. Mol Cell Biol. 1996;16:4710-6 pubmed
    ..Taken together, these data indicate that a single tyrosine of the IL-9 receptor, required for activation of three different STAT proteins, is necessary for distinct activities of this cytokine, including proliferative responses. ..
  50. Hauber H, Manoukian J, Nguyen L, Sobol S, Levitt R, Holroyd K, et al. Increased expression of interleukin-9, interleukin-9 receptor, and the calcium-activated chloride channel hCLCA1 in the upper airways of patients with cystic fibrosis. Laryngoscope. 2003;113:1037-42 pubmed
    ..These preliminary findings suggest that hCLCA1 might be an interesting new therapeutic target to control mucus overproduction in airway disease in patients with cystic fibrosis. ..
  51. Vink A, Warnier G, Brombacher F, Renauld J. Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population. J Exp Med. 1999;189:1413-23 pubmed
    ..The increase of antigen-specific antibody concentration in immunized mice suggests that these B-1 cells are directly or indirectly involved in antibody responses in IL-9 transgenic mice. ..
  52. Longphre M, Li D, Gallup M, Drori E, Ordoñez C, Redman T, et al. Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells. J Clin Invest. 1999;104:1375-82 pubmed
    ..Furthermore, recombinant IL-9, but not IL-5 or IL-13, stimulated mucin synthesis. These results indicate that IL-9 may account for as much as 50-60% of the mucin-stimulating activity of lung fluids in allergic airway disease. ..
  53. McMillan S, Bishop B, Townsend M, McKenzie A, Lloyd C. The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. J Exp Med. 2002;195:51-7 pubmed
    ..These findings indicate that IL-9 is not obligatory for the development of eosinophilia and AHR, and imply that other Th2 cytokines can act in a compensatory fashion. ..