Environmental Science and Pollution Research

, Volume 24, Issue 28, pp 22579–22586 | Cite as

A pilot study comparing T-regulatory cell function among healthy children in different areas of Gansu, China

  • Panhong Gou
  • Xiaoru Chang
  • Zhonghui Ye
  • Yueli Yao
  • Patton Khuu Nguyen
  • Sally Katharine Hammond
  • Junling WangEmail author
  • Sa LiuEmail author
Research Article


Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions. Air pollutions in Lanzhou and Lintao, Gansu Province, were measured from December 2015 to June 2016. Healthy children were recruited from both cities and enrolled in this pilot study. Demographic information was collected by questionnaires. Blood samples were collected. Peripheral blood Treg cells were analyzed for Treg cells percentage by flow cytometry. Gene expression of forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), and interleukin 35 (IL35) were examined by reverse transcription-polymerase chain reaction (RT-PCR). The results indicated PAH concentration (as sum of 16 PAHs) in Lintao was over two times higher than that was in Lanzhou (707 vs. 326 ng/m3), whereas PM2.5 concentration was comparable in two cities (55.3 in Lintao vs. 65.7 μg/m3 in Lanzhou). Notably, we observed lower gene expressions for Foxp3 (P < 0.05), IL35 (P < 0.05), and TGF-β, in children living in Lintao, suggesting an impairment of Treg cells function potentially associated with higher PAH exposure in Lintao. However, no significant difference was observed in Treg cells % among CD4+ T cells between Lanzhou and Lintao groups.


Air pollution Immune system Treg cells Immune system Cytokine 



This study was supported by Chau Hoi Shuen Women in Science Program. The authors wish to thank the hospital staff for their assistance in blood sample collection and the children from both cities for their participation.

Author contribution

Sa Liu, Junling Wang, and S. Katharine Hammond conceived and designed the study. Panhong Gou, Zhonghui Ye, and Yueli Yao carried out the data collection. Panhong Gou, Xiaoru Chang, and Patton Khuu Nguyen conducted the labor test. Panhong Gou analyzed the data and developed the initial draft of the paper. All authors reviewed and provided input to the writing, editing, and finalization of the paper.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. Arnold J, Zimmerman B, Li M, Lairmore MD, Green PL (2008) Human T-cell leukemia virus type-1 antisense-encoded gene, Hbz, promotes T-lymphocyte proliferation. Blood 112:3788–3797CrossRefGoogle Scholar
  2. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179:572–578CrossRefGoogle Scholar
  3. Bartel DP (2004) MicroRNAs genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefGoogle Scholar
  4. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27:20–21CrossRefGoogle Scholar
  5. Chaturvedi V, Collison LW, Guy CS, Workman CJ, Vignali DA (2011) Cutting edge: human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J Immunol 186:6661–6666CrossRefGoogle Scholar
  6. Chen W, Konkel JE (2010) TGF-beta and ‘adaptive’ Foxp3(+) regulatory T cells. J Mol Cell Biol 2:30–36CrossRefGoogle Scholar
  7. Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M (2006) A role for Dicer in immune regulation. J Exp Med 203:2519–2527CrossRefGoogle Scholar
  8. Cohen AC, Nadeau KC, Tu W, Hwa V, Dionis K, Bezrodnik L, Teper A, Gaillard M, Heinrich J, Krensky AM, Rosenfeld RG, Lewis DB (2006) Cutting edge: decreased accumulation and regulatory function of CD41 CD25(high) T cells in human STAT5b deficiency. J Immunol 177:2770–2774CrossRefGoogle Scholar
  9. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569CrossRefGoogle Scholar
  10. Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, Finkelstein D, Forbes K, Workman CJ, Brown SA, Rehg JE, Jones ML, Ni HT, Artis D, Turk MJ, Vignali DA (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11:1093–1101CrossRefGoogle Scholar
  11. Fragale A, Gabriele L, Stellacci E, Borghi P, Perrotti E, Ilari R, Lanciotti A, Remoli AL, Venditti M, Belardelli F, Battistini A (2008) IFN regulatory factor-1 negatively regulates CD4+CD25+ regulatory T cell differentiation by repressing Foxp3 expression. Immunology 181:1673–1682CrossRefGoogle Scholar
  12. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144CrossRefGoogle Scholar
  13. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, Holl JL (2011) The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics 128:E9–E17CrossRefGoogle Scholar
  14. Hew KM, Walker AI, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth EM, Mann JK, Pratt B, Balmes J, Hammond SK, Eisen EA, Nadeau KC (2015) Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clin Exp Allergy 45:238–248CrossRefGoogle Scholar
  15. Hill JA, Benoist C, Mathis D (2007) Treg cells: guardians for life. Nat Immunol 8:124–125CrossRefGoogle Scholar
  16. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061CrossRefGoogle Scholar
  17. Huter EN, Punkosdy GA, Glass DD, Cheng LI, Ward JM, Shevach EM (2008) TGF-b-induced Foxp3+ regulatory T cells rescue scurfy mice. Eur J Immunol 38:1814–1821CrossRefGoogle Scholar
  18. IARC (1987) Overall Evaluations of Carcinogenicity. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans, Supplement 7.Google Scholar
  19. Kavouras IG, Tsapakis KP, Lagoudaki M, Stephanou E, Von EG, Baer D, Oyola P (2001) Source apportionment of urban particulate aliphatic and polynuclear aromatic hydrocarbons (PAHs) using multivariate methods. Environ Sci Technol 35:2288–2294CrossRefGoogle Scholar
  20. Li W, Wang C, Wang H, Chen J, Shen H, Shen G, Huang Y, Wang R, Wang B, Zhang Y, Chen H, Chen Y, Su S, Lin N, Tang J, Li Q, Wang X, Liu J, Tao S (2014) Atmospheric polycyclic aromatic hydrocarbons in rural and urban areas of northern China. Environ Pollut 192:83–90CrossRefGoogle Scholar
  21. Lin SS, Huang Y, Wang CY, Ren AG (2016) Polycyclic aromatic hydrocarbons exposure and birth defects. Chin J Prev Med 50:563–568Google Scholar
  22. Mao J, Zhao MT, Whitworth KM, Spate LD, Walters EM, O'Gorman C, Lee K, Samuel MS, Murphy CN, Wells K, Rivera RM, Prather RS (2015) Oxamflatin treatment enhances cloned porcine embryo development and nuclear reprogramming. Cell Reprogram 17:28–40CrossRefGoogle Scholar
  23. Marson A, Kretschmer K, Frampton GM, Jacobsen ES, Polansky JK, MacIsaac KD, Levine SS, Fraenkel E, von Boehmer H, Young RA (2007) Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445:931–935CrossRefGoogle Scholar
  24. Miller RL, Ho SM (2008) Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med 177:567–573CrossRefGoogle Scholar
  25. Moorman JE, Akinbami LJ, Bailey CM, Zahran HS, King ME, Johnson CA, Liu X (2012) National surveillance of asthma: United States, 2001–2010. Vital Health Stat 35:1–58Google Scholar
  26. Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I (2010) Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 126:845–852 e810CrossRefGoogle Scholar
  27. Nguyen KD, Fohner A, Booker JD, Dong C, Krensky AM, Nadeau KC (2008) XCL1 enhances regulatory activities of CD4+CD25+CD127-T cell in human allergic asthma. J Immunol 181:5386–5395CrossRefGoogle Scholar
  28. Noth EM, Lurmann F, Northcross A, Perrino C, Vaughn D, Hammond SK (2016) Spatial and temporal distribution of polycyclic aromatic hydrocarbons and elemental carbon in Bakersfield, California. Air Qual Atmos Health 9:899–908CrossRefGoogle Scholar
  29. Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM (2009) Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4:e4488CrossRefGoogle Scholar
  30. Perez L, Declercq C, Iniguez C, Aguilera I, Badaloni C, Ballester F, Bouland C, Chanel O, Cirarda FB, Forastiere F, Forsberg B, Haluza D, Hedlund B, Cambra K, Lacasana M, Moshammer H, Otorepec P, Rodriguez-Barranco M, Medina S, Kunzli N (2013) Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network). Eur Respir J 42:594–605CrossRefGoogle Scholar
  31. Pleil JD, Vette AF, Johnson BA, Rappaport SM (2004) Air levels of carcinogenic polycyclic aromatic hydrocarbons after the World Trade Center disaster. Proc Natl Acad Sci U S A 101:11685–11688CrossRefGoogle Scholar
  32. Sakaguchi S, Wing K, Yamaguchi T (2009) Dynamics of peripheral tolerance and immune regulation mediated by Treg. Eur J Immunol 39:2331–2336CrossRefGoogle Scholar
  33. Shimon S, Tomoyuki Y, Takashi N, Masahiro O (2008) Regulatory T cells and immune tolerance. Cell 133:775–787CrossRefGoogle Scholar
  34. Takeuchi Y, Nishikawa H (2016) Roles of regulatory T cells in cancer immunity. Int Immunol 28:401–409CrossRefGoogle Scholar
  35. Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont LJ, Ceuppens JL, Bullens DM (2006) Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 61:202–208CrossRefGoogle Scholar
  36. Verhasselt V, Milcent V, Cazareth J, Kanda A, Fleury S, Dombrowicz D, Glaichenhaus N, Julia V (2008) Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat Med 14:170–175CrossRefGoogle Scholar
  37. Wang M, Zheng S, Wang S, Tao Y, Shang K (2012) A time-series study on the relationship between gaseous air pollutants and daily hospitalization of respiratory disease in Lanzhou City. J Hyg Res 41:771–775Google Scholar
  38. Whitehead GS, Wilson RH, Nakano K, Burch LH, Nakano H, Cook DN (2012) IL-35 production by inducible costimulator (ICOS)–positive regulatory T cells reverses established IL-17–dependent allergic airways disease. J Allergy Clin Immunol 129:207–215.e205CrossRefGoogle Scholar
  39. Woodfolk JA (2007) T-cell responses to allergens. J Allergy Clin Immunol 119:280–294CrossRefGoogle Scholar
  40. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA (2001) A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol 166:7282–7289CrossRefGoogle Scholar
  41. 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 445:936–940CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Panhong Gou
    • 1
  • Xiaoru Chang
    • 1
  • Zhonghui Ye
    • 1
  • Yueli Yao
    • 1
  • Patton Khuu Nguyen
    • 2
  • Sally Katharine Hammond
    • 2
  • Junling Wang
    • 1
    Email author
  • Sa Liu
    • 2
    Email author
  1. 1.Department of Toxicology, School of Public HealthLanzhou UniversityLanzhouChina
  2. 2.Division of Environmental Health Sciences, School of Public HealthUniversity of California, BerkeleyBerkeleyUSA

Personalised recommendations