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

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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.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (nos. 81070408, 81070411, 30570779, 30770922, 81070407, 30971278, and 81070396), the National 973 Basic Research Program of China (grant 2011CB503906), Foundation for the Author of National Excellent Doctoral Dissertation of PR China (no. 200561), Program for New Century Excellent Talents in University (NCET-07-0514), Key Project of Chinese Ministry of Education (109097), Key Clinical Research Project of Public Health Ministry of China 2010–2012, Outstanding Young Scientist Research Award Foundation of Shandong Province (2008BSO3009, BS2010YY024), Natural Science Foundation of Shandong Province (ZR2009CM001, ZR2010HQ002), Clinical Medicine Center Foundation of Shandong Province, Leading Medical Professionals Foundation of Shandong Province, Tai Shan Scholar Foundation, Independent Innovation Foundation of Shandong University (no. 2009TS053), and State Program of National Natural Science Foundation of China for Innovative Research Group (81021001).

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Authors and Affiliations

  1. Haematology Oncology Centre, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, Shandong, 250012, China

    Chun-yan Wang, Yan Shi, Ya-nan Min, Xiao-juan Zhu, Jun Peng, Xiao-yuan Dong, Ping Qin, Jian-zhi Sun & Ming Hou

  2. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, 250012, China

    Jun Peng & Ming Hou

  3. Department of General Medicine, Second Hospital affiliated to Shandong University, Jinan, 250033, China

    Chun-yan Wang

  4. Department of Hematology, Second Hospital of Shandong University , Jinan, 250033, China

    Cheng-shan Guo

  5. Department of General Medicine, Provincial Hospital affiliated to Shandong University, Jinan, 250021, China

    Xiao-juan Zhu

  6. Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China

    Yan Shi

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  1. Chun-yan Wang
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  2. Yan Shi
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Correspondence to Yan Shi.

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Chun-yan Wang, Yan Shi, and Ya-nan Min contributed equally to this work.

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Wang, Cy., Shi, Y., Min, Yn. et al. Decreased IDO Activity and Increased TTS Expression Break Immune Tolerance in Patients with Immune Thrombocytopenia. J Clin Immunol 31, 643–649 (2011). https://doi.org/10.1007/s10875-011-9525-7

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  • DOI: https://doi.org/10.1007/s10875-011-9525-7

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