Skip to content
2000
image of Restoring Immune Balance in Allergic Airway Inflammation: Yanghe Pingchuan Granules Regulate Th17/Treg via PD-1/PD-L1 Pathway

Abstract

Introduction

Allergic airway inflammation (AAI), an asthma-like condition, is characterized by Th17/Treg imbalance and PD-1/PD-L1 pathway dysregulation. Yanghe Pingchuan Granules (YP) formulation is clinically used to treat asthma, but its immunomodulatory mechanisms remain unclear.

Methods

Using an AAI rat model, the effects of YP were assessed. Flow cytometry was carried out to analyze Th17/Treg proportions. Additionally, the expression levels of Foxp3, ROR?t, IL-10, IL-17, and TGF-1 were measured. PD-L1 siRNA knockdown and overexpression studies were performed to elucidate the role of the pathway.

Results

YP treatment restored the Th17/Treg balance by reducing Th17 and increasing Treg cells. It upregulated IL-10 and TGF-1 while downregulating IL-17. YP inhibited the PD-1/PD-L1 pathway, correlating with improved immune balance and reduced inflammation. PD-L1 modulation confirmed its role in mediating the effects of YP on cellular and cytokine profiles.

Discussion

The findings indicated that the therapeutic action of YP involves modulation of the Th17/Treg imbalance, likely through inhibition of the PD-1/PD-L1 pathway, thereby shifting thecytokine milieu from a pro- to an anti-inflammatory state.

Conclusion

YP alleviates AAI by modulating the PD-1/PD-L1 pathway to restore Th17/Treg balance and suppress inflammation, thereby revealing its potential immunomodulatory mechanism.

Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073412055251107212524
2026-01-09
2026-01-29
Loading full text...

Full text loading...

References

  1. Aegerter H. Lambrecht B.N. The pathology of Asthma: What is obstructing our view? Annu. Rev. Pathol. 2023 18 1 387 409 10.1146/annurev‑pathol‑042220‑015902 36270294
    [Google Scholar]
  2. Cao Y. Chen S. Chen X. Zou W. Liu Z. Wu Y. Hu S. Global trends in the incidence and mortality of asthma from 1990 to 2019: An age-period-cohort analysis using the global burden of disease study 2019. Front. Public Health 2022 10 1036674 10.3389/fpubh.2022.1036674 36483262
    [Google Scholar]
  3. Garg R. Piplani M. Singh Y. Joshi Y. Epidemiology, pathophysiology, and pharmacological status of asthma. Curr. Respir. Med. Rev. 2022 18 4 247 258 10.2174/1573398X18666220526164329
    [Google Scholar]
  4. Wang Y. Liu L. Immunological factors, important players in the development of asthma. BMC Immunol. 2024 25 1 50 10.1186/s12865‑024‑00644‑w 39060923
    [Google Scholar]
  5. Eger K. Amelink M. Hashimoto S. Hekking P.P. Longo C. Bel E.H. Overuse of oral corticosteroids, underuse of inhaled corticosteroids, and implications for biologic therapy in Asthma. Respiration 2022 101 2 116 121 10.1159/000518514 34535586
    [Google Scholar]
  6. Al Heialy S. Ramakrishnan R.K. Hamid Q. Recent advances in the immunopathogenesis of severe asthma. J. Allergy Clin. Immunol. 2022 149 2 455 465 10.1016/j.jaci.2021.12.765 35125181
    [Google Scholar]
  7. Busse W.W. Kraft M. Current unmet needs and potential solutions to uncontrolled asthma. Eur. Respir. Rev. 2022 31 163 210176 10.1183/16000617.0176‑2021 35082128
    [Google Scholar]
  8. Kuruvilla M.E. Lee F.E.H. Lee G.B. Understanding Asthma phenotypes, endotypes, and mechanisms of disease. Clin. Rev. Allergy Immunol. 2019 56 2 219 233 10.1007/s12016‑018‑8712‑1 30206782
    [Google Scholar]
  9. Ricciardolo F.L.M. Sprio A.E. Baroso A. Gallo F. Riccardi E. Bertolini F. Carriero V. Arrigo E. Ciprandi G. Characterization of T2-Low and T2-high asthma phenotypes in real-life. Biomedicines 2021 9 11 1684 10.3390/biomedicines9111684 34829913
    [Google Scholar]
  10. Dutta A. Venkataganesh H. Love P.E. New insights into epigenetic regulation of T cell differentiation. Cells 2021 10 12 3459 10.3390/cells10123459 34943965
    [Google Scholar]
  11. Liao Y. Cavalcante R.G. Waller J.B. Deng F. Scruggs A.M. Huang Y.J. Atasoy U. Chen Y. Huang S.K. Differences in the DNA methylome of T cells in adults with asthma of varying severity. Clin. Epigenetics 2024 16 1 139 10.1186/s13148‑024‑01750‑7 39380119
    [Google Scholar]
  12. Aun M. Bonamichi-Santos R. Arantes-Costa F.M. Kalil J. Giavina-Bianchi P. Animal models of asthma: Utility and limitations. J. Asthma Allergy 2017 10 293 301 10.2147/JAA.S121092 29158683
    [Google Scholar]
  13. Alessandrini F. Musiol S. Schneider E. Blanco-Pérez F. Albrecht M. Mimicking antigen-driven asthma in rodent models—How close can we get? Front. Immunol. 2020 11 575936 10.3389/fimmu.2020.575936 33101301
    [Google Scholar]
  14. Agrawal D.K. Shao Z. Pathogenesis of allergic airway inflammation. Curr. Allergy Asthma Rep. 2010 10 1 39 48 10.1007/s11882‑009‑0081‑7 20425513
    [Google Scholar]
  15. Hirose K. Iwata A. Tamachi T. Nakajima H. Allergic airway inflammation: Key players beyond the Th2 cell pathway. Immunol. Rev. 2017 278 1 145 161 10.1111/imr.12540 28658544
    [Google Scholar]
  16. Lu K. Li C. Men J. Xu B. Chen Y. Yan P. Gai Z. Zhang Q. Zhang L. Traditional Chinese medicine to improve immune imbalance of asthma: Focus on the adjustment of gut microbiota. Front. Microbiol. 2024 15 1409128 10.3389/fmicb.2024.1409128 39411430
    [Google Scholar]
  17. Zhang C. Zhang L.H. Wu Y.F. Lai T.W. Wang H.S. Xiao H. Che L.Q. Ying S.M. Li W. Chen Z.H. Shen H.H. Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation and remodeling in a murine model of chronic asthma. Sci. Rep. 2016 6 1 21515 10.1038/srep21515 26861679
    [Google Scholar]
  18. Lee M.Y. Lee J.A. Seo C.S. Ha H. Lee N.H. Shin H.K. Protective effects of Mentha haplocalyx ethanol extract (MH) in a mouse model of allergic asthma. Phytother. Res. 2011 25 6 863 869 10.1002/ptr.3341 21108485
    [Google Scholar]
  19. Gu X. Chen Y. Qian P. He T. Wu Y. Lin W. Zheng J. Hong M. Cimifugin suppresses type 2 airway inflammation by binding to SPR and regulating its protein expression in a non-enzymatic manner. Phytomedicine 2023 111 154657 10.1016/j.phymed.2023.154657 36701995
    [Google Scholar]
  20. Pan L. Chen Y. Jiang Y. Sun Y. Han Y. Wang Y. Yanghe Pingchuan granules alleviate airway inflammation in bronchial asthma and inhibit pyroptosis by blocking the TLR4/NF-κB/NRLP3 signaling pathway. Mediators Inflamm. 2022 2022 1 9 10.1155/2022/6561048 36091667
    [Google Scholar]
  21. Pan L. Gong C. Chen Y. Jiang Y. Sun Y. He B. Duan X. Han Y. Wang Y. Yanghe Pingchuan granules mitigates oxidative stress and inflammation in a bronchial asthma rat model: Role of the IKK/IκB/NF-κB signalling pathway. Ann. Med. Surg. 2024 86 1 212 218 10.1097/MS9.0000000000001553 38222706
    [Google Scholar]
  22. Zhou B. Liu H. Jia X. The role and mechanisms of traditional Chinese medicine for airway inflammation and remodeling in asthma: Overview and progress. Front. Pharmacol. 2022 13 917256 10.3389/fphar.2022.917256 35910345
    [Google Scholar]
  23. Pan L. Han Y. Wang Y. Chen Q. Wu Y. Sun Y. Mechanism of Yanghe Pingchuan granules treatment for airway remodeling in asthma. Drug Des. Devel. Ther. 2018 12 1941 1951 10.2147/DDDT.S159428 29983548
    [Google Scholar]
  24. Zhu H. Wang K. Yang L. Xu Q. Ren F. Liu X. Yanghe Pingchuan granule promotes BMSCs homing in asthmatic rats by upregulating miR-139-5p and downregulating Notch1/Hes1 pathway. Nan Fang Yi Ke Da Xue Xue Bao 2020 40 12 1703 1711 33380402
    [Google Scholar]
  25. Zhang B. Zeng M. Zhang Q. Wang R. Jia J. Cao B. Liu M. Guo P. Zhang Y. Zheng X. Feng W. Ephedrae Herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance. Mol. Immunol. 2022 152 14 26 10.1016/j.molimm.2022.09.009 36215828
    [Google Scholar]
  26. Wang W. Jiang T. Zhu Z. Cui J. Zhu L. Ma Z. Dexamethasone suppresses allergic rhinitis and amplifies CD4 + Foxp3 + regulatory T cells in vitro. Int. Forum Allergy Rhinol. 2015 5 10 900 906 10.1002/alr.21579 26086746
    [Google Scholar]
  27. Wu S. Luo Y. Zeng Z. Yu Y. Zhang S. Hu Y. Chen L. Determination of internal controls for quantitative gene expression of Spodoptera litura under microbial pesticide stress. Sci. Rep. 2024 14 1 6143 10.1038/s41598‑024‑56724‑9 38480844
    [Google Scholar]
  28. Zazara D.E. Wegmann M. Giannou A.D. Hierweger A.M. Alawi M. Thiele K. Huber S. Pincus M. Muntau A.C. Solano M.E. Arck P.C. A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice. J. Allergy Clin. Immunol. 2020 145 6 1641 1654 10.1016/j.jaci.2020.01.050 32305348
    [Google Scholar]
  29. Wu Y. Di X. Zhao M. Li H. Bai L. Wang K. The role of the NLRP3 inflammasome in chronic inflammation in asthma and chronic obstructive pulmonary disease. Immun. Inflamm. Dis. 2022 10 12 e750 10.1002/iid3.750 36444628
    [Google Scholar]
  30. Liu L. Gao Y. Si Y. Liu B. Liu X. Li G. Wang R. MALT1 in asthma children: A potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance‐mediated inflammation. J. Clin. Lab. Anal. 2022 36 5 e24379 10.1002/jcla.24379 35353938
    [Google Scholar]
  31. Lopes F.D.T.Q.S. Tibério I.F.L.C. Leme A. Fairclough L. Editorial: The importance of Th17/Treg imbalance in asthma and COPD development and progression. Front. Immunol. 2022 13 1025215 10.3389/fimmu.2022.1025215 36211425
    [Google Scholar]
  32. Liu D. Tan Y. Bajinka O. Wang L. Tang Z. Th17/IL-17 axis regulated by airway microbes get involved in the development of Asthma. Curr. Allergy Asthma Rep. 2020 20 4 11 10.1007/s11882‑020‑00903‑x 32172346
    [Google Scholar]
  33. Li C. Sheng A. Jia X. Zeng Z. Zhang X. Zhao W. Zhang W. Th17/Treg dysregulation in allergic asthmatic children is associated with elevated notch expression. J. Asthma 2018 55 1 1 7 10.1080/02770903.2016.1266494 28463581
    [Google Scholar]
  34. Xuan J. Changes in serum CCR5 and eotaxin levels in patients with bronchial asthma and their impact on Th17/Treg cell balance. J. Immunol. 2021 37 11 6
    [Google Scholar]
  35. Wang C. Huang C.F. Li M. Sodium houttuynia alleviates airway inflammation in asthmatic mice by regulating FoxP3/RORγT expression and reversing Treg/Th17 cell imbalance. Int. Immunopharmacol. 2022 103 108487 10.1016/j.intimp.2021.108487 34959187
    [Google Scholar]
  36. Lu J. Wu J. Mao L. Xu H. Wang S. Revisiting PD-1/PD-L pathway in T and B cell response: Beyond immunosuppression. Cytokine Growth Factor Rev. 2022 67 58 65 10.1016/j.cytogfr.2022.07.003 35850949
    [Google Scholar]
  37. Tang Q. Chen Y. Li X. Long S. Shi Y. Yu Y. Wu W. Han L. Wang S. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front. Immunol. 2022 13 964442 10.3389/fimmu.2022.964442 36177034
    [Google Scholar]
  38. Parvez A. Choudhary F. Mudgal P. Khan R. Qureshi K.A. Farooqi H. Aspatwar A. PD-1 and PD-L1: Architects of immune symphony and immunotherapy breakthroughs in cancer treatment. Front. Immunol. 2023 14 1296341 10.3389/fimmu.2023.1296341 38106415
    [Google Scholar]
  39. Matsuda K. Miyoshi H. Hiraoka K. Hamada T. Yoshida S. Ishibashi Y. Haraguchi T. Shiba N. Ohshima K. Clinicopathological value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in synovium of patients with rheumatoid arthritis. Clin. Exp. Med. 2018 18 4 487 494 10.1007/s10238‑018‑0515‑4 29961175
    [Google Scholar]
  40. McGee H.S. Yagita H. Shao Z. Agrawal D.K. Programmed Death-1 antibody blocks therapeutic effects of T-regulatory cells in cockroach antigen-induced allergic asthma. Am. J. Respir. Cell Mol. Biol. 2010 43 4 432 442 10.1165/rcmb.2009‑0258OC 19901343
    [Google Scholar]
  41. Xi X. Liu J.M. Guo J.Y. Correlation of PD-1/PD-L1 signaling pathway with Treg/Th17 imbalance from asthmatic children. Int. Arch. Allergy Immunol. 2018 176 3-4 255 267 10.1159/000489338 29874664
    [Google Scholar]
  42. Acevedo N. Alashkar Alhamwe B. Caraballo L. Ding M. Ferrante A. Garn H. Garssen J. Hii C.S. Irvine J. Llinás-Caballero K. López J.F. Miethe S. Perveen K. Pogge von Strandmann E. Sokolowska M. Potaczek D.P. van Esch B.C.A.M. Perinatal and early-life nutrition, epigenetics, and allergy. Nutrients 2021 13 3 724 10.3390/nu13030724 33668787
    [Google Scholar]
  43. Esch B.C.A.M. Porbahaie M. Abbring S. Garssen J. Potaczek D.P. Savelkoul H.F.J. Neerven R.J.J. The impact of milk and its components on epigenetic programming of immune function in early life and beyond: Implications for allergy and asthma. Front. Immunol. 2020 11 2141 10.3389/fimmu.2020.02141 33193294
    [Google Scholar]
  44. Arpaia N. Campbell C. Fan X. Dikiy S. van der Veeken J. deRoos P. Liu H. Cross J.R. Pfeffer K. Coffer P.J. Rudensky A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013 504 7480 451 455 10.1038/nature12726 24226773
    [Google Scholar]
  45. Furusawa Y. Obata Y. Fukuda S. Endo T.A. Nakato G. Takahashi D. Nakanishi Y. Uetake C. Kato K. Kato T. Takahashi M. Fukuda N.N. Murakami S. Miyauchi E. Hino S. Atarashi K. Onawa S. Fujimura Y. Lockett T. Clarke J.M. Topping D.L. Tomita M. Hori S. Ohara O. Morita T. Koseki H. Kikuchi J. Honda K. Hase K. Ohno H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013 504 7480 446 450 10.1038/nature12721 24226770
    [Google Scholar]
  46. Hu M. Alashkar Alhamwe B. Santner-Nanan B. Miethe S. Harb H. Renz H. Potaczek D.P. Nanan R.K. Short-chain fatty acids augment differentiation and function of human induced regulatory T cells. Int. J. Mol. Sci. 2022 23 10 5740 10.3390/ijms23105740 35628549
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073412055251107212524
Loading
/content/journals/cchts/10.2174/0113862073412055251107212524
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test