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Annals of Hematology

, Volume 98, Issue 8, pp 1845–1854 | Cite as

The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia

  • Yumeng Lu
  • Luya Cheng
  • Feng Li
  • Lili Ji
  • Xia Shao
  • Boting Wu
  • Yanxia Zhan
  • Chanjuan Liu
  • Zhihui Min
  • Yang Ke
  • Lihua Sun
  • Hao ChenEmail author
  • Yunfeng ChengEmail author
Original Article
  • 74 Downloads

Abstract

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25 Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25 Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25 Teff cells. CD4+CD25 Teff cells had increased A2AR expression after treatment.

Keywords

Immune thrombocytopenia Regulatory T cell CD39 Adenosine receptor A2AR Dexamethasone 

Notes

Author contribution

YL and YC conceived the study; YL, LC, FL, LJ, and YC performed the literature review, and drafted and revised the manuscript; YL and YC contributed to the critical revision of the manuscript; YL, YZ, LC, XS, BW, CL, ZM, YK, LS, and HC performed the experiments and analyzed the data. All authors read and approved the final manuscript.

Funding information

This study was supported by grants from the National Natural Science Foundation of China(81870098, 81600090, 81470282,81500090), the Science and Technology Commission of Shanghai Municipality (18ZR1407200), and the Shanghai Municipal Health Bureau (20134Y117, 20144Y0194), and grant from Zhongshan Hospital (2015ZSYXGG09).

Compliance with ethical standards

The study was approved by local Medical Ethics Committees of Zhongshan Hospital, Fudan University. Written informed consent was obtained from each patient enrolled in the study.

Competing interests

The authors declare that they have no conflict of interest.

Data sharing statement

Data sharing: no additional data available

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Copyright information

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

Authors and Affiliations

  1. 1.Department of HematologyZhongshan Hospital Fudan UniversityShanghaiChina
  2. 2.Department of Hematology, Shanghai Tenth People’s HospitalTongji UniversityShanghaiChina
  3. 3.Department of Hematology, Zhongshan Hospital Qingpu BranchFudan UniversiyShanghaiChina
  4. 4.Department of Transfusion MedicineZhongshan Hospital Fudan UniversityShanghaiChina
  5. 5.Institute of Clinical Science, Zhongshan HospitalFudan UniversityShanghaiChina
  6. 6.Shanghai Institute of Clinical BioinformaticsFudan University Center for Clinical BioinformaticsShanghaiChina
  7. 7.Department of Thoracic Surgery, Zhongshan Hospital Xuhui BranchFudan UniversityShanghaiChina
  8. 8.Institute of Clinical Science, Department of Hematology, Zhongshan HospitalFudan UniversityShanghaiChina

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