, Volume 37, Issue 4, pp 1070–1077 | Cite as

IL-25 Promotes Th2 Immunity Responses in Airway Inflammation of Asthmatic Mice via Activation of Dendritic Cells

  • Li Hongjia
  • Zhang Caiqing
  • Lu Degan
  • Liu Fen
  • Wang Chao
  • Wu Jinxiang
  • Dong Liang


Allergic asthma occurs as a consequence of inappropriate immunologic inflammation to allergens and characterized by Th2 adaptive immune response. Recent studies indicated that interleukin (IL)-25, a member of the IL-17 cytokine family, had been implicated in inducing Th2 cell-dependent inflammation in airway epithelium and IL-25-deficient mice exhibit impaired Th2 immunity responses; however, how these cytokines influence innate immune responses remains poorly understood. In this study, we used ovalbumin (OVA) sensitization and challenge to induce the murine asthmatic model and confirmed by histological analysis of lung tissues and serum levels of total and OVA-specific immunoglobulin (Ig)-E. The expression of IL-25 was detected by quantitative real-time PCR and immunohistochemistry, respectively, and the dendritic cells (DCs) activation was detected by levels of CD80 and CD86 in bronchoalveolar lavage fluid (BALF) by flow cytometry. The mice sensitized and challenged with OVA showed high expression of IL-25 in both mRNA and protein levels in lungs. We detected the expression of CD80 and CD86 in BALF was also increased. A tight correlation between IL-25 mRNA and other Th2 cells producing cytokines such as IL-4, IL-5, and IL-13 in BALF was identified. Furthermore, when the asthmatic mice were treated with inhaled corticosteroids, the inflammatory cells infiltration and the inflammatory cytokines secretion were significantly decreased. In this study, we show that IL-25 promoted the accumulation of co-stimulatory molecules of CD80 and CD86 on DCs and then induced the differentiation of prime naive CD4+ T cells to become proinflammatory Th2 cells and promoted Th2 cytokine responses in OVA-induced airway inflammation. The ability of IL-25 to promote the activation and differentiation of DCs population was identified as a link between the IL-17 cytokine family and the innate immune response and suggested a previously unrecognized innate immune pathway that promotes Th2 cytokine responses in asthmatic airway inflammation. Inhaled corticosteroids might be capable of inhibiting the promotion of IL-25 and present a promising strategy for the treatment of asthma


interleukin-25 asthma airway inflammation Th2 immunity Responses dendritic cells 



The authors thank Dr. Rutao Cui for supplying the IL25 antibody and Rong Wang (Key Laboratory of Cardiovascular Remodeling and Function Research of Chinese Ministry of Education and Public Health, Shandong University Qilu Hospital) for their excellent technical assistance. This work was supported by the Science and Technology Foundation of Shandong Province (2012GGB14068), the Natural and Science Foundation of Shandong Province (ZR2011HM020) and The National Natural Science Foundation of China (81270072). We also thank Dr. Xiaotian Chang (Medical Research Center of Qianfoshan Hospital, Shandong University) and Margaret Mysz, PhD (Loyola University, Chicago, USA), for revising the manuscript.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.


  1. 1.
    Antus, B. 2012. Clinical application of induced and spontaneous sputum in asthma and chronic obstructive pulmonary disease. Orvosi Hetilap 153(47): 1847–1854.PubMedCrossRefGoogle Scholar
  2. 2.
    Yang, Z., V. Grinchuk, J.F. Urban Jr., et al. 2013. Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity. PLoS ONE 8(3): e59441.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Kim, J.Y., M.S. Jeong, K.Y. Park, et al. 2013. Aggravation of atopic dermatitis-like symptoms by consecutive low concentration of formaldehyde exposure in NC/Nga mice. Experimental Dermatology 22(3): 219–221.PubMedCrossRefGoogle Scholar
  4. 4.
    Wang, Y.H., P. Angkasekwinai, N. Lu, et al. 2007. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC activated Th2 memory cells. Journal of Experimental Medicine 204(8): 1837–1847.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Silverman, J., S.P. Baker, and C.W. Lidz. 2012. A self-assessment survey of the Institutional Animal Care and Use Committee: Part 1. Animal welfare and protocol compliance. Laboratory Animals 41(8): 230–235.CrossRefGoogle Scholar
  6. 6.
    Marwick, J.A., C.S. Stevenson, K.F. Chung, et al. 2010. Cigarette smoke exposure alters mSin3a and Mi-2alpha/beta Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function. Inflammation 16(7): 33–34.CrossRefGoogle Scholar
  7. 7.
    Chan, Y.K., P.F. Davis, S.D. Poppitt, et al. 2012. Influence of tail versus cardiac sampling on blood glucose and lipid profiles in mice. Laboratory Animals 46(2): 142–147.PubMedCrossRefGoogle Scholar
  8. 8.
    Neill, D.R., S.H. Wong, A. Bellosi, et al. 2010. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464(7293): 1367–1370.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Groves, A.M., A.J. Gow, C.B. Massa, et al. 2012. Prolonged injury and altered lung function after ozone inhalation in mice with chronic lung inflammation. American Journal of Respiratory Cell and Molecular Biology 47(6): 776–783.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Kaiko, G.E., and P.S. Foster. 2011. New insights into the generation of Th2 immunity and potential therapeutic targets for the treatment of asthma. Current Opinion in Allergy Clinical Immunology 11(1): 39–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Stock, P., V. Lombardi, V. Kohlrautz, et al. 2009. Induction of airway hyper-reactivity by IL-25 is dependent on a subset of invariant NKT cells expressing IL-17RB. Journal of Immunology 182(8): 5116–5122.CrossRefGoogle Scholar
  12. 12.
    Barlow, J.L., R.J. Flynn, S.J. Ballantyne, et al. 2011. Reciprocal expression of IL-25 and IL-17A is important for allergic airways hyper-reactivity. Clinical & Experimental Allergy 41(10): 1447–1455.CrossRefGoogle Scholar
  13. 13.
    Zaph, C. 2008. Y. Du, S. A. Saenz, et al. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. Journal of Experimental Medicine 205(10): 2191–2198.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Liu, R., J. Bai, G. Xu, et al. 2013. Multi-allergen challenge stimulates steriod-resistant airway inflammation via NF-κB-mediated IL-8 expression. Inflammation 36(4): 845–854.PubMedCrossRefGoogle Scholar
  15. 15.
    Hayashi, H., A. Kawakita, S. Okazaki, et al. 2013. IL-17A/F modulates fibrocyte functions in cooperation with CD40-mediated signaling. Inflammation 36(4): 830–838.PubMedCrossRefGoogle Scholar
  16. 16.
    Saenz, S.A., M.C. Siracusa, J.G. Perrigoue, et al. 2010. IL-25 elicits a multi-potent progenitor cell population that promotes Th2 cytokine responses. Nature 464(7293): 1362–1366.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Gregory, L.G., C.P. Jones, S.A. Walker, et al. 2013. IL-25 drives remodeling in allergic airways disease induced by house dust mite. Thorax 68(1): 82–90.PubMedCentralPubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pulmonary Disease, Qianfoshan HospitalShandong UniversityJinanChina
  2. 2.Department of Pulmonary DiseasesQilu Hospital of Shandong UniversityJinanChina

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