Skip to main content

Advertisement

SpringerLink
Log in

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Masoli, M., D. Fabian, S. Holt, and R. Beasley. 2004. The global burden of asthma: Executive summary of the GINA DisSDination Committee report. Allergy. 59: 469–478.

    Article  Google Scholar 

  2. Hirose, K., A. Iwata, T. Tamachi, and H. Nakajima. 2017. Allergic airway inflammation: Key players beyond the Th2 cell pathway. Immunological Reviews 278: 145–161.

    Article  CAS  Google Scholar 

  3. Foster, P.S., S. Maltby, H.F. Rosenberg, H.L. Tay, S.P. Hogan, A.M. Collison, et al. 2017. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunological Reviews 278: 20–40.

    Article  CAS  Google Scholar 

  4. Akdis, M., and C.A. Akdis. 2009. Therapeutic manipulation of immune tolerance in allergic disease. Nature Reviews. Drug Discovery 8: 645–660.

    Article  CAS  Google Scholar 

  5. Akdis, C.A. 2012. Therapies for allergic inflammation: Refining strategies to induce tolerance. Nature Medicine 18: 736–749.

    Article  CAS  Google Scholar 

  6. Akdis, C.A., T. Blesken, M. Akdis, B. Wuthrich, and K. Blaser. 1998. Role of interleukin 10 in specific immunotherapy. The Journal of Clinical Investigation 102: 98–106.

    Article  CAS  Google Scholar 

  7. Akkoc, T., D. Genc, N. Zibandeh, and T. Akkoc. 2018. Intranasal ovalbumin immunotherapy with mycobacterial adjuvant promotes regulatory T cell accumulation in lung tissues. Microbiology and Immunology 62: 531–540.

    Article  CAS  Google Scholar 

  8. Globinska, A., T. Boonpiyathad, P. Satitsuksanoa, M. Kleuskens, W. van de Veen, M. Sokolowska, et al. 2018. Mechanisms of allergen-specific immunotherapy: Diverse mechanisms of immune tolerance to allergens. Annals of Allergy, Asthma & Immunology 121: 306–312.

    Article  CAS  Google Scholar 

  9. Yukselen, A., and S.G. Kendirli. 2014. Role of immunotherapy in the treatment of allergic asthma. World Journal of Clinical Cases 2: 859–865.

    Article  Google Scholar 

  10. Ma, A., and B.A. Malynn. 2012. A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nature Reviews. Immunology 12: 774–785.

    Article  CAS  Google Scholar 

  11. Huang, P., X.R. Geng, G. Yang, C. Chen, Z. Liu, and P.C. Yang. 2012. Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function. Cellular Physiology and Biochemistry 30: 702–710.

    Article  CAS  Google Scholar 

  12. Ventura, S., F. Cano, Y. Kannan, F. Breyer, M.J. Pattison, M.S. Wilson, and S.C. Ley. 2018. A20-binding inhibitor of NF-kappaB (ABIN) 2 negatively regulates allergic airway inflammation. The Journal of Experimental Medicine 215: 2737–2747.

    Article  CAS  Google Scholar 

  13. Kang, N.I., H.Y. Yoon, Y.R. Lee, M. Won, M.J. Chung, J.W. Park, et al. 2009. A20 attenuates allergic airway inflammation in mice. Journal of Immunology 183: 1488–1495.

    Article  CAS  Google Scholar 

  14. Schuijs, M.J., M.A. Willart, K. Vergote, D. Gras, K. Deswarte, M.J. Ege, F.B. Madeira, R. Beyaert, G. van Loo, F. Bracher, E. von Mutius, P. Chanez, B.N. Lambrecht, and H. Hammad. 2015. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science. 349: 1106–1110.

    Article  CAS  Google Scholar 

  15. Salari, F., A.R. Varasteh, F. Vahedi, M. Hashemi, and M. Sankian. 2015. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice. International Immunopharmacology 29: 672–678.

    Article  CAS  Google Scholar 

  16. Joshi, V.B., A. Adamcakova-Dodd, X. Jing, A. Wongrakpanich, K.N. Gibson-Corley, P.S. Thorne, and A.K. Salem. 2014. Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy. The AAPS Journal 16: 975–985.

    Article  CAS  Google Scholar 

  17. Trindade, R.A., P.K. Kiyohara, P.S. de Araujo, and D.C.M. Bueno. 2012. PLGA microspheres containing bee venom proteins for preventive immunotherapy. International Journal of Pharmaceutics 423: 124–133.

    Article  CAS  Google Scholar 

  18. Bosnjak, B., B. Stelzmueller, K.J. Erb, and M.M. Epstein. 2011. Treatment of allergic asthma: Modulation of Th2 cells and their responses. Respiratory Research 12: 114.

    Article  CAS  Google Scholar 

  19. Kim, S.B., A.Y. Lee, J.M. Chun, A.R. Lee, H.S. Kim, Y.S. Seo, et al. 2019. Anthriscus sylvestris root extract reduces allergic lung inflammation by regulating interferon regulatory factor 4-mediated Th2 cell activation. Journal of Ethnopharmacology 232: 165–175.

    Article  Google Scholar 

  20. Youm, J., H. Lee, H.B. Chang, J. Jeon, M.H. Yoon, J.Y. Woo, M.S. Choi, Y. Hwang, S. Seong, K. Na, and J. Yoon. 2017. Justicia procumbens extract (DW2008) selectively suppresses Th2 cytokines in splenocytes and ameliorates ovalbumin-induced airway inflammation in a mouse model of asthma. Biological & Pharmaceutical Bulletin 40: 1416–1422.

    Article  CAS  Google Scholar 

  21. Luo, X.Q., F. Ma, S. Wang, M.Z. Zhao, J.B. Shao, X.R. Geng, et al. 2019. Interleukin-5 induces apoptotic defects in CD4(+) T cells of patients with allergic rhinitis. Journal of Leukocyte Biology 105: 719–727.

    Article  CAS  Google Scholar 

  22. De Jong, W.H., and P.J. Borm. 2008. Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine 3: 133–149.

    Article  Google Scholar 

  23. Choi, S., J. Lee, P. Kumar, K.Y. Lee, and S.K. Lee. 2011. Single chain variable fragment CD7 antibody conjugated PLGA/HDAC inhibitor immuno-nanoparticles: Developing human T cell-specific nano-technology for delivery of therapeutic drugs targeting latent HIV. Journal of Control Release 152 (Suppl 1): e9–e10.

    Article  CAS  Google Scholar 

  24. Reddy, K.S., B.R. Rashmi, H.J. Dechamma, S. Gopalakrishna, N. Banumathi, V.V. Suryanarayana, et al. 2012. Cationic microparticle [poly(D,L-lactide-co-glycolide)]-coated DNA vaccination induces a long-term immune response against foot and mouth disease in guinea pigs. The Journal of Gene Medicine 14: 348–352.

    Article  CAS  Google Scholar 

  25. Kostadinova, A.I., J. Middelburg, M. Ciulla, J. Garssen, W.E. Hennink, L. Knippels, C. van Nostrum, and L.E.M. Willemsen. 2018. PLGA nanoparticles loaded with beta-lactoglobulin-derived peptides modulate mucosal immunity and may facilitate cow’s milk allergy prevention. European Journal of Pharmacology 818: 211–220.

    Article  CAS  Google Scholar 

  26. Khademi, F., M. Derakhshan, A. Yousefi-Avarvand, A. Najafi, and M. Tafaghodi. 2018. A novel antigen of mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity. Microbial Pathogenesis 125: 507–513.

    Article  CAS  Google Scholar 

  27. Sadat, T.M.F., K. Nejati-Koshki, A. Akbarzadeh, M.R. Yamchi, M. Milani, N. Zarghami, et al. 2014. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific Journal of Cancer Prevention 15: 517–535.

    Article  Google Scholar 

  28. Matsuda, M., Y. Morie, H. Oze, K. Doi, T. Tsutsumi, J. Hamaguchi, M. Inaba, and T. Nabe. 2018. Phenotype analyses of IL-10-producing Foxp3(-) CD4(+) T cells increased by subcutaneous immunotherapy in allergic airway inflammation. International Immunopharmacology 61: 297–305.

    Article  CAS  Google Scholar 

  29. Bohm, L., J. Maxeiner, H. Meyer-Martin, S. Reuter, S. Finotto, M. Klein, et al. 2015. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma. Journal of Immunology 194: 887–897.

    Article  Google Scholar 

Download references

Funding

This study was supported by grants from the National Nature and Science Foundation of China (81701589), the Miao-Miao plan of Shenzhen Hospital, Southern Medical University (2017MM05), and Guangdong Nature Science Foundation (2016A030310248; 2014A020212569).

Author information

Author notes

  1. Xiang-Qian Luo, Jian-Wen Zhong and Shu-Yao Qiu contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, 1033 Qinghu Blvd, Shenzhen, 518101, China

    Xiang-Qian Luo, Jian-Wen Zhong, Shu-Yao Qiu, Min Zhi, Li-Qiang Yang, Yi-Long Zhou, Fen-Xuan Zhou, Da-Bo Liu & Li-Hua Mo

  2. The Research Center of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, China

    Ping-Chang Yang

Authors
  1. Xiang-Qian Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian-Wen Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu-Yao Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Zhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Qiang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi-Long Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fen-Xuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ping-Chang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Da-Bo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Li-Hua Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XQL, JWZ, SYQ, LQY, ZYL, MZ, and FXZ performed the experiments, analyzed the data, and reviewed the manuscript. LHM, DBL, and PCY organized and supervised the experiments. LHM and DBL designed the project and prepared the manuscript. PCY reviewed and edited the manuscript.

Corresponding author

Correspondence to Li-Hua Mo.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luo, XQ., Zhong, JW., Qiu, SY. et al. A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model. Inflammation 43, 953–961 (2020). https://doi.org/10.1007/s10753-020-01181-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-020-01181-5

KEY WORDS

Search

Navigation