From Bench to Bedside: Therapeutic Potential of Interleukin-9 in the Treatment of Asthma

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2017 Mar 30

PMID 28352305

Citations 9

Authors

Fang Gong

Yu-Hong Pan

Xuan Huang

Hua-Yan Zhu

Dong-Lin Jiang

Affiliations

Soon will be listed here.

Abstract

Initially identified as a T cell and mast cell growth factor, interleukin (IL)-9 has long been recognized as an important mediator of asthma. Recently, accumulating results from transgenic mice demonstrated that systemic or lung-specific overexpression of IL-9 caused asthma-associated symptoms. Moreover, anti-mIL-9 antibody (Ab) blocking treatment alleviated disease in animal models of asthma. In light of the large quantity of data from the murine models, MEDI-528, a humanized anti-IL-9 monoclonal Ab has been produced to assess the activity of IL-9 on human asthma. In order to ascertain whether it is a successful translation from bench to bedside, the biological features of IL-9 were evaluated and up-to-date information regarding the role of IL-9 in different experimental murine models and human asthma were summarized.

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References

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(12):1763-70. DOI: 10.1038/sj.onc.1206253. View

Noguchi E, Shibasaki M, Arinami T, Takeda K, Maki T, Miyamoto T . Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population. Am J Respir Crit Care Med. 1997; 156(5):1390-3. DOI: 10.1164/ajrccm.156.5.9702084. View

Hultner L, Druez C, Moeller J, Uyttenhove C, Schmitt E, Rude E . Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9). Eur J Immunol. 1990; 20(6):1413-6. DOI: 10.1002/eji.1830200632. View

Temann U, Geba G, Rankin J, Flavell R . Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness. J Exp Med. 1998; 188(7):1307-20. PMC: 2212487. DOI: 10.1084/jem.188.7.1307. View

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(18):6934-8. PMC: 282093. DOI: 10.1073/pnas.85.18.6934. View

Russell S, Johnston J, Noguchi M, Kawamura M, Bacon C, Friedmann M . Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. Science. 1994; 266(5187):1042-5. DOI: 10.1126/science.7973658. View

Baldini M, Lohman I, Halonen M, Erickson R, Holt P, Martinez F . A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol. 1999; 20(5):976-83. DOI: 10.1165/ajrcmb.20.5.3494. View

Hornakova T, Staerk J, Royer Y, Flex E, Tartaglia M, Constantinescu S . Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimers. J Biol Chem. 2009; 284(11):6773-81. PMC: 2652315. DOI: 10.1074/jbc.M807531200. View

McLane M, Haczku A, van de Rijn M, Weiss C, Ferrante V, MacDonald D . Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice. Am J Respir Cell Mol Biol. 1998; 19(5):713-20. DOI: 10.1165/ajrcmb.19.5.3457. View

10.

Erpenbeck V, Hohlfeld J, Discher M, Krentel H, Hagenberg A, Braun A . Increased expression of interleukin-9 messenger RNA after segmental allergen challenge in allergic asthmatics. Chest. 2003; 123(3 Suppl):370S. View

11.

Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel R . 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(12):1347-55. PMC: 2999006. DOI: 10.1038/ni.1677. View

12.

Sherkat R, Yazdani R, Ganjalikhani Hakemi M, Homayouni V, Farahani R, Hosseini M . Innate lymphoid cells and cytokines of the novel subtypes of helper T cells in asthma. Asia Pac Allergy. 2014; 4(4):212-21. PMC: 4215431. DOI: 10.5415/apallergy.2014.4.4.212. View

13.

Hultner L, Kolsch S, Stassen M, Kaspers U, Kremer J, Mailhammer R . In activated mast cells, IL-1 up-regulates the production of several Th2-related cytokines including IL-9. J Immunol. 2000; 164(11):5556-63. DOI: 10.4049/jimmunol.164.11.5556. View

14.

Hoppenot D, Malakauskas K, Lavinskiene S, Bajoriuniene I, Kalinauskaite V, Sakalauskas R . Peripheral blood Th9 cells and eosinophil apoptosis in asthma patients. Medicina (Kaunas). 2015; 51(1):10-7. DOI: 10.1016/j.medici.2015.01.001. View

15.

Pae S, Cho J, Dayan S, Miller M, Pemberton A, Broide D . Chronic allergen challenge induces bronchial mast cell accumulation in BALB/c but not C57BL/6 mice and is independent of IL-9. Immunogenetics. 2010; 62(8):499-506. PMC: 2910299. DOI: 10.1007/s00251-010-0452-1. View

16.

Erpenbeck V, Hohlfeld J, Volkmann B, Hagenberg A, Geldmacher H, Braun A . 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(6):1319-27. DOI: 10.1067/mai.2003.1485. View

17.

Melen E, Gullsten H, Zucchelli M, Lindstedt A, Nyberg F, Wickman M . Sex specific protective effects of interleukin-9 receptor haplotypes on childhood wheezing and sensitisation. J Med Genet. 2004; 41(12):e123. PMC: 1735647. DOI: 10.1136/jmg.2004.023135. View

18.

Noelle R, Nowak E . Cellular sources and immune functions of interleukin-9. Nat Rev Immunol. 2010; 10(10):683-7. PMC: 3828627. DOI: 10.1038/nri2848. View

19.

Elyaman W, Bradshaw E, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J . 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):12885-90. PMC: 2722314. DOI: 10.1073/pnas.0812530106. View

20.

Postma D, Bleecker E, Amelung P, Holroyd K, Xu J, Panhuysen C . Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy. N Engl J Med. 1995; 333(14):894-900. DOI: 10.1056/NEJM199510053331402. View