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Decreased Treg-derived miR-181a and miR-155 correlated with reduced number and function of Treg cells in allergic rhinitis children

  • Wenlong LiuEmail author
  • Hong Ouyang
  • Qingxiang Zeng
  • Renzhong Luo
  • Gen LuEmail author
Rhinology

Abstract

Background

Regulatory cells (Tregs) have been proved to be deeply involved in allergic airway inflammation. This study aims to evaluate the expression of miRNA in children with AR and their association with Tregs as well as the severity of AR.

Methods

Twenty-five AR children and 20 healthy children were enrolled in this study. The Treg-cell percentage and expression of IL-10 and TGF-β were detected by flow cytometry and enzyme-linked immunosorbent assay. The microRNA microarray analysis in purified Tregs was performed and differentially expressed microRNAs were confirmed by quantitative polymerase chain reaction (qPCR).

Results

Children with AR had lower percentage of Tregs and expression of IL-10 and TGF-beta compared with control children. We found that significantly lower levels of miR-155 and miR-181a in Tregs from AR than healthy controls. Furthermore, intracellular miR-155 and miR-181a level were positively correlated with percentage of Tregs and expression of IL-10 and TGF-beta. Similarly, total nasal severity scores (TNSS) were found to be negatively correlated with miR-155 and miR-181a levels.

Conclusion

Decreased Treg-derived miR-181a and miR-155 were correlated with reduced number and function of Tregs in AR children. The intracellular miR-155 and miR-181a levels may serve as predictors of disease severity in childhood AR.

Keywords

Allergic rhinitis Children Regulatory T cells miR-181a miR-155 

Notes

Funding

This study was supported by grants from the National Natural Science Grant of China (No. 81500772), the Guangdong Province Natural Science Grant (Nos. 2014A030310216, 2017A030310150), and the Pearl River S&T Nova Program of Guangzhou (No. 201710010085).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all guardians of children included in the study.

References

  1. 1.
    Solelhac G, Charpin D (2014) Management of allergis rhinitis. F1000Prime Rep 6:1–6CrossRefGoogle Scholar
  2. 2.
    Tharpe CA, Kemp SF (2015) Pediatric allergic rhinitis. Immunol Allergy Clin N Am 35:185–198CrossRefGoogle Scholar
  3. 3.
    Scadding GK (2015) Optimal management of allergic rhinitis. Arch Dis Child 100:576–582CrossRefPubMedGoogle Scholar
  4. 4.
    Wisniewski JA, Borish L (2011) Novel cytokines and cytokine-producing T cells in allergic disorders. Allergy Asthma Proc 32:83–94CrossRefPubMedGoogle Scholar
  5. 5.
    Lewkowich IP, Herman NS, Schleifer KW et al (2005) CD4 + CD25 + T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med 202:1549–1561CrossRefPubMedGoogle Scholar
  6. 6.
    Kearley J, Barker JE, Robinson DS, Lloyd CM (2005) Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4 + CD25 + regulatory T cells is interleukin 10 dependent. J Exp Med 202:1539–1547CrossRefPubMedGoogle Scholar
  7. 7.
    Askenasy N, Kaminitz A, Yarkoni S (2008) Mechanisms of T regulatory cell function. Autoimmun Rev 7:370–375CrossRefPubMedGoogle Scholar
  8. 8.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  9. 9.
    Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T, Yoshimura A, Baltimore D, Rudensky AY (2010) Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142:914–929CrossRefPubMedGoogle Scholar
  10. 10.
    Liston A, Lu LF, O’Carroll D, Tarakhovsky A, Rudensky AY (2008) Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med 205:1993–2004CrossRefPubMedGoogle Scholar
  11. 11.
    Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA (2008) Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205:1983–1991CrossRefPubMedGoogle Scholar
  12. 12.
    Kelada S, Sethupathy P, Okoye IS, Kistasis E, Czieso S, White SD, Chou D, Martens C, Ricklefs SM, Virtaneva K, Sturdevant DE, Porcella SF, Belkaid Y, Wynn TA, Wilson MS (2013) miR-182 and miR-10a are key regulators of Treg specialisation and stability during Schistosome and Leishmania-associated inflammation. PLoS Pathog 9:e1003451CrossRefPubMedGoogle Scholar
  13. 13.
    Kohlhaas S, Garden OA, Scudamore C, Turner M, Okkenhaug K, Vigorito E (2009) Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells. J Immunol 182:2578–2582CrossRefPubMedGoogle Scholar
  14. 14.
    Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY (2007) Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445:936–940CrossRefPubMedGoogle Scholar
  15. 15.
    Shaoqing Y, Ruxin Z, Guojun L, Zhiqiang Y, Hua H, Shudong Y et al (2011) Microarray analysis of differentially expressed microRNAs in allergic rhinitis. Am J Rhinol Allergy 25:e242–e246CrossRefPubMedGoogle Scholar
  16. 16.
    Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schünemann HJ (2010) Global allergy and asthma European Network. Grading of recommendations assessment, development and evaluation working Group. AllergicRhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 126:466–476CrossRefPubMedGoogle Scholar
  17. 17.
    Liu W, Xia W, Fan Y, Wang H, Zuo K, Lai Y et al (2012) Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis. J Allergy Clin Immunol 130:1416–1418.e6CrossRefPubMedGoogle Scholar
  18. 18.
    Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4 + CD25- naive T cells to CD4 + CD25 + regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886CrossRefPubMedGoogle Scholar
  19. 19.
    Ciprandi G, Fenoglio D, Cirillo I, Vizzaccaro A, Ferrero A, Tosca MA, Puppo F (2005) Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report. Ann Allergy Asthma Immunol 95:38–44CrossRefPubMedGoogle Scholar
  20. 20.
    O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D (2010) Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 10:111–122CrossRefPubMedGoogle Scholar
  21. 21.
    Suojalehto H, Lindström I, Majuri ML, Mitts C, Karjalainen J, Wolff H et al (2014) Altered microRNA expression of nasal mucosa in long-term asthma and allergic rhinitis. Int Arch Allergy Immunol 163:168–178CrossRefPubMedGoogle Scholar
  22. 22.
    Levänen B, Bhakta NR, Torregrosa Paredes P, Barbeau R, Hiltbrunner S, Pollack JL et al (2013) Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients. J Allergy Clin Immunol 131:894–903.e8CrossRefPubMedGoogle Scholar
  23. 23.
    Ruggiero T, Trabucchi M, De Santa F, Zupo S, Harfe BD, McManus MT, Rosenfeld MG, Briata P, Gherzi R (2009) LPS induces KH-type splicing regulatory protein-dependent processing of micro-RNA-155 precursors in macrophages. FASEB J 23:2898–2908CrossRefPubMedGoogle Scholar
  24. 24.
    Blüml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, Koenders MI, van den Berg WB, Smolen J, Redlich K (2011) Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 63:1281–1288CrossRefPubMedGoogle Scholar
  25. 25.
    Li QJ, Chau J, Ebert PJ et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161CrossRefPubMedGoogle Scholar
  26. 26.
    Neilson JR, Zheng GX, Burge CB, Sharp PA (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 21:578–589CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OtolaryngologyGuangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityGuangzhouChina
  2. 2.Department of Otolaryngology, Renhe HospitalThree Gorges UniversityYi ChangChina
  3. 3.Department of Respiratory Medicine, Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhouChina

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