Decreased IDO Activity and Increased TTS Expression Break Immune Tolerance in Patients with Immune Thrombocytopenia

  • Chun-yan Wang
  • Yan Shi
  • Ya-nan Min
  • Xiao-juan Zhu
  • Cheng-shan Guo
  • Jun Peng
  • Xiao-yuan Dong
  • Ping Qin
  • Jian-zhi Sun
  • Ming Hou
Article

Abstract

Introduction

Indoleamine 2,3-dioxygenase (IDO) can promote peripheral immune tolerance and control autoimmune responses through tryptophan catabolism. Tryptophanyl-tRNA synthetase (TTS) can protect T cells from IDO-mediated cell injury. Impaired IDO-mediated tryptophan catabolism has been observed in some autoimmune diseases.

Materials and Methods

The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry.

Results

Compared with healthy controls, the PBMCs of patients with immune thrombocytopenia (ITP) had significantly increased expressions of IDO and TTS, especially IDO. However, the plasma tryptophan concentration was significantly elevated, and kynurenine concentration was significantly reduced in ITP patients. In CD4+ and CD8+ T cells of the ITP patients, IDO expressions were significantly lower than those in healthy controls, but in CD19+ and CD14+ cells, IDO expression significantly increased. Conversely, TTS expressions in CD4+ and CD8+ T cells of the ITP patients were significantly higher than those in healthy controls, but there was no difference either in CD19+ or CD14+ cells.

Conclusion

These results suggest that the activity of IDO enzyme is insufficient in ITP patients. Increased TTS expressions from CD4+ and CD8+ T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in ITP patients.

Keywords

Indoleamine 2,3-dioxygenase tryptophanyl-tRNA synthetase immune thrombocytopenic purpura 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Chun-yan Wang
    • 1
    • 3
  • Yan Shi
    • 1
    • 6
  • Ya-nan Min
    • 1
  • Xiao-juan Zhu
    • 1
    • 5
  • Cheng-shan Guo
    • 4
  • Jun Peng
    • 1
    • 2
  • Xiao-yuan Dong
    • 1
  • Ping Qin
    • 1
  • Jian-zhi Sun
    • 1
  • Ming Hou
    • 1
    • 2
  1. 1.Haematology Oncology Centre, Qilu HospitalShandong UniversityJinanChina
  2. 2.Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of Education and Chinese Ministry of HealthJinanChina
  3. 3.Department of General MedicineSecond Hospital affiliated to Shandong UniversityJinanChina
  4. 4.Department of HematologySecond Hospital of Shandong University JinanChina
  5. 5.Department of General MedicineProvincial Hospital affiliated to Shandong UniversityJinanChina
  6. 6.Department of Hematology, Qilu HospitalShandong UniversityJinanPeople’s Republic of China

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