Expression of CD39 MRNA is Altered in the Peripheral Blood of Patients with Allergic Asthma

Overview

Journal Biomed Rep

Specialty Biochemistry

Date 2014 Mar 21

PMID 24649072

Citations 5

Authors

Lin-Lin Wang

Ping-Hua Tang

Chao-Guo Shi

Ying-Huan Wan

Wei Tang

Xia-Xiao Hou

Na-Li Pan

Yu-Bao Shi

Qin-Lian Tao

Affiliations

Soon will be listed here.

Abstract

The ectoenzyme CD39 hydrolyzes extracellular adenosine 5'-triphosphate (ATP), which possesses pro-inflammatory properties. However, the role of CD39 in allergic asthma has not been fully elucidated. A total of 18 patients with persistent asthma who were allergic to house dust mites and 19 healthy volunteers were enrolled in this study. The expression of CD39, GATA3, RAR-related orphan receptor γ (ROR-γt) and forkhead box P3 (FoxP3) mRNA in peripheral blood mononuclear cells (PBMCs) was determined by SYBR-Green I quantitative polymerase chain reaction (qPCR). The cytokines interleukin (IL)-4, IL-17A, transforming growth factor β (TGF-β) and DP.sIgE were detected by enzyme-linked immunosorbent assay. Our data demonstrated that the expression of CD39 mRNA in PBMCs from asthmatic patients was significantly lower compared to that in normal controls [(1.49±0.59)×10 vs. (2.17±0.77)×10, respectively; P<0.01]. CD39 mRNA was negatively correlated with serum IL-4, IL-17A and GATA3 expression (r=-0.468, P<0.05; r=-0.550, P<0.05; and r=-0.424, P<0.01, respectively) and positively correlated with FoxP3 and TGF-β expression (r=0.373, P<0.05; and r=0.425, P<0.05, respectively). There was no obvious correlation between CD39 and ROR-γt expression (r=-0.259, P=0.122). These data suggested that CD39 mRNA expression was downregulated in allergic asthma, which was positively correlated with serum IL-4, IL-17A and GATA3 expression and negatively correlated with serum TGF-β and FoxP3 expression, whereas there was no correlation with ROR-γt. Therefore, it was hypothesized that CD39 may participate in the occurrence and progression of allergic asthma.

Citing Articles

IL-4 prevents adenosine-mediated immunoregulation by inhibiting CD39 expression.

Fang F, Cao W, Mu Y, Okuyama H, Li L, Qiu J JCI Insight. 2022; 7(12).

PMID: 35730568 PMC: 9309057. DOI: 10.1172/jci.insight.157509.

Reducing Lung ATP Levels and Alleviating Asthmatic Airway Inflammation through Adeno-Associated Viral Vector-Mediated CD39 Expression.

Huang Y, Chen J, Wu C, Hsu C, Ko A, Chen L Biomedicines. 2021; 9(6).

PMID: 34201190 PMC: 8228057. DOI: 10.3390/biomedicines9060656.

Long-lived regulatory T cells generated during severe bronchiolitis in infancy influence later progression to asthma.

Lynch J, Werder R, Curren B, Sikder M, Ullah A, Sebina I Mucosal Immunol. 2020; 13(4):652-664.

PMID: 32066837 DOI: 10.1038/s41385-020-0268-8.

The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.

Antonioli L, Blandizzi C, Pacher P, Hasko G Pharmacol Rev. 2019; 71(3):345-382.

PMID: 31235653 PMC: 6592405. DOI: 10.1124/pr.117.014878.

The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature.

Tang W, Shang Y, Xiao B, Wen P, Lyu R, Ning K J Healthc Eng. 2018; 2018:9363820.

PMID: 30210753 PMC: 6126072. DOI: 10.1155/2018/9363820.

References

Deaglio S, Dwyer K, Gao W, Friedman D, Usheva A, Erat A . Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007; 204(6):1257-65. PMC: 2118603. DOI: 10.1084/jem.20062512. View

Curotto de Lafaille M, Kutchukhidze N, Shen S, Ding Y, Yee H, Lafaille J . Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation. Immunity. 2008; 29(1):114-26. DOI: 10.1016/j.immuni.2008.05.010. View

Weaver C, Harrington L, Mangan P, Gavrieli M, Murphy K . Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 2006; 24(6):677-688. DOI: 10.1016/j.immuni.2006.06.002. View

Shi Y, Shi G, Wan H, Jiang L, Ai X, Zhu H . Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. Chin Med J (Engl). 2011; 124(13):1951-6. View

Huang S, Apasov S, Koshiba M, Sitkovsky M . Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood. 1997; 90(4):1600-10. View

Fletcher J, Lonergan R, Costelloe L, Kinsella K, Moran B, OFarrelly C . CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol. 2009; 183(11):7602-10. DOI: 10.4049/jimmunol.0901881. View

Maliszewski C, Delespesse G, Schoenborn M, Armitage R, Fanslow W, Nakajima T . The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization. J Immunol. 1994; 153(8):3574-83. View

Zhu J, Yamane H, Cote-Sierra J, Guo L, Paul W . GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 2006; 16(1):3-10. DOI: 10.1038/sj.cr.7310002. View

Zhou L, Chong M, Littman D . Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009; 30(5):646-55. DOI: 10.1016/j.immuni.2009.05.001. View

10.

Koziak K, Sevigny J, Robson S, Siegel J, Kaczmarek E . Analysis of CD39/ATP diphosphohydrolase (ATPDase) expression in endothelial cells, platelets and leukocytes. Thromb Haemost. 1999; 82(5):1538-44. View

11.

Erpenbeck V, Hagenberg A, Krentel H, Discher M, Braun A, Hohlfeld J . Regulation of GATA-3, c-maf and T-bet mRNA expression in bronchoalveolar lavage cells and bronchial biopsies after segmental allergen challenge. Int Arch Allergy Immunol. 2006; 139(4):306-16. DOI: 10.1159/000091602. View

12.

Ivanov I, McKenzie B, Zhou L, Tadokoro C, Lepelley A, Lafaille J . The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006; 126(6):1121-33. DOI: 10.1016/j.cell.2006.07.035. View

13.

Dong C . TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008; 8(5):337-48. DOI: 10.1038/nri2295. View

14.

Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R . Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110(4):1225-32. DOI: 10.1182/blood-2006-12-064527. View

15.

Imai M, Goepfert C, Kaczmarek E, Robson S . CD39 modulates IL-1 release from activated endothelial cells. Biochem Biophys Res Commun. 2000; 270(1):272-8. DOI: 10.1006/bbrc.2000.2410. View

16.

Michel M, Pang D, Haque S, Potocnik A, Pennington D, Hayday A . Interleukin 7 (IL-7) selectively promotes mouse and human IL-17-producing γδ cells. Proc Natl Acad Sci U S A. 2012; 109(43):17549-54. PMC: 3491488. DOI: 10.1073/pnas.1204327109. View

17.

Shevach E . CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol. 2002; 2(6):389-400. DOI: 10.1038/nri821. View

18.

Josefowicz S, Rudensky A . Control of regulatory T cell lineage commitment and maintenance. Immunity. 2009; 30(5):616-25. PMC: 4410181. DOI: 10.1016/j.immuni.2009.04.009. View

19.

Ohta A, Sitkovsky M . Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 2002; 414(6866):916-20. DOI: 10.1038/414916a. View

20.

Warny M, Aboudola S, Robson S, Sevigny J, Communi D, Soltoff S . P2Y(6) nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide. J Biol Chem. 2001; 276(28):26051-6. DOI: 10.1074/jbc.M102568200. View