Skip to main content
SpringerLink
Log in

Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice

  • Acupuncture Research
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice.

Methods

BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay.

Results

Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01).

Conclusion

Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.

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

Similar content being viewed by others

References

  1. Erle DJ, Sheppard D. The cell biology of asthma. J Cell Biol 2014;205:621–631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol 2015;16:45–56.

    Article  CAS  PubMed  Google Scholar 

  3. Moldaver DM, Larche M, Rudulier CD. An update on lymphocyte subtypes in asthma and airway disease. Chest 2017;151:1122–1130.

    Article  PubMed  Google Scholar 

  4. Lambrecht BN, Hamida H. Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Immunology 2012;30:243–270.

    Article  CAS  Google Scholar 

  5. Shi YH, Shi GC, Wan HY, Jiang LH, Ai XY, Zhu HX, et al. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. Chin Med J 2011;124:1951–1956.

    CAS  PubMed  Google Scholar 

  6. Mielke K, Herdegen T. JNK and p38 stresskinases— degenerative effectors of signal-transduction-cascades in the nervous system. Prog Neurobiol 2000;61:45–60.

    Article  CAS  PubMed  Google Scholar 

  7. Subhashini, Chauhan PS, Dash D, Paul BN, Singh R. Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma. Int Immunopharmacol 2016;31:200–206.

    Article  CAS  PubMed  Google Scholar 

  8. Chialda L, Zhang M, Brune K, Pahl A. Inhibitors of mitogenactivated protein kinases differentially regulate costimulated T cell cytokine production and mouse airway eosinophilia. Respir Res 2005;6:36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Acupuncture. NIH consensus statement. Available at https://doi.org/consensus.nih.gov/1997/1997acupuncture107html.htm

  10. Fung KP, Chow OK, So SY. Attenuation of exercise-induced asthma by acupuncture. Lancet 1986;328:1419–1422.

    Article  Google Scholar 

  11. World Health Organization. Acupuncture: review and analysis of reports on controlled clinical trials. Available at https://doi.org/apps.who.int/bookorders/anglais/detart1.jsp?sesslan=1&codlan=1&codcol=93&codcch=196

  12. Han J. Observation on effect of acupuncture at Yuji (LU 10) on the pulmonary function of patients with bronchial asthma and immediate efficacy of relieving asthma. China Med Abstr (Int Med, Chin) 2012;32:891–894.

    Google Scholar 

  13. Lewith GT, Watkins AD. Unconventional therapies in asthma: an overview. Allergy 1996;51:761–769.

    Article  CAS  PubMed  Google Scholar 

  14. Carneiro ER, Xavier RA, De Castro MA, Do Nascimento CM, Silveira VL. Electroacupuncture promotes a decrease in inflammatory response associated with Th1/Th2 cytokines, nitric oxide and leukotriene B4 modulation in experimental asthma. Cytokine 2010;50:335–340.

    Article  CAS  PubMed  Google Scholar 

  15. Dong M, Xie SY, Li FC, Lu N, Wei XP. Is acupuncture better than sham acupuncture for attenuated airway inflammation and regulated cytokines produced by diverse Th subtypes in chronic OVA inhalation in asthma induced mice. Eur J Integr Med 2015;7:485–491.

    Article  Google Scholar 

  16. Yang YQ, Chen HP, Wang Y, Yin LM, Xu YD, Ran J. Considerations for use of acupuncture as supplemental therapy for patients with allergic asthma. Clin Rev Allergy Immunol 2013;44:254–261.

    Article  PubMed  Google Scholar 

  17. Wei B, Zhang H, Li L, Li M, Shang Y. T helper 17 cells and regulatory T-cell imbalance in paediatric patients with asthma. J Int Med Res 2011;39:1293–1305.

    Article  CAS  PubMed  Google Scholar 

  18. Wills-Karp M. Interleukin-13 in asthma pathogenesis. Immunol Rev 2004;202:175–190.

    Article  CAS  PubMed  Google Scholar 

  19. Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature 2008;453:1051–1057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 2008;181:4089–4097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Holt PG, Strickland DH, Wikstrom ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 2008;8:142–152.

    Article  CAS  PubMed  Google Scholar 

  22. Ji X, Li J, Xu L, Wang W, Luo M, Luo S, et al. IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-beta1 to induce bronchial epithelial-mesenchymal transition (EMT). Int J Clin Exp Pathol 2013;6:1481–1492.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Huang MT, Dai YS, Chou YB, Juan YH, Wang CC, Chiang BL. Regulatory T cells negatively regulate neovasculature of airway remodeling via DLL4-Notch signaling. J Immunol 2009;183:4745–4754.

    Article  CAS  PubMed  Google Scholar 

  24. Wills-Kar M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science 1998;282:2258–2261.

    Article  Google Scholar 

  25. Bellini A, Marini MA, Bianchetti L, Barczyk M, Schmidt M, Mattoli S. Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients. Mucos Immunol 2012;5:140–149.

    Article  CAS  Google Scholar 

  26. Zhao J, Lloyd CM, Noble A. Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cellmediated tolerance and contribute to airway remodeling. Mucos Immunol 2013;6:335–346.

    Article  CAS  Google Scholar 

  27. Su X, Pan J, Bai F, Yuan H, Dong N, Li D, et al. IL-27 attenuates airway inflammation in a mouse asthma model via the STAT1 and GADD45gamma/p38 MAPK pathways. J Transl Med 2016;14:283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, et al. Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax 2008;63:784–790.

    Article  CAS  PubMed  Google Scholar 

  29. Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal 2000;12:1–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gumei Community Health Center of Minhang District, Shanghai, 201102, China

    Ming Dong

  2. Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Wen-qian Wang, Mi-hui Li, Fei Xu, Jie Cui, Jing-cheng Dong & Ying Wei

  3. Institutes of Integrative Medicine of Fudan University, Shanghai, 200040, China

    Wen-qian Wang, Mi-hui Li, Fei Xu, Jie Cui, Jing-cheng Dong & Ying Wei

  4. Department of Pediatric Neurological Rehabilitation, Maternal and Child Health Hospital of Dengfeng, Dengfeng, 452470, Henan Province, China

    Juan Chen

Authors
  1. Ming Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wen-qian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mi-hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jing-cheng Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ying Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying Wei.

Additional information

Supported by the National Natural Science Foundation of China (No. 81403476)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dong, M., Wang, Wq., Chen, J. et al. Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice. Chin. J. Integr. Med. 25, 617–624 (2019). https://doi.org/10.1007/s11655-018-3055-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-018-3055-6

Keywords

Search

Navigation