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Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia

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Abstract

Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO+ DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO+ DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO+ DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.

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Acknowledgments

This work was supported by grants from Tai Shan Scholar Foundation, National Natural Science Foundation of China (numbers 81170475, 30800491, 30801258, 30971278, 81070396, 81070408, 81070407, 81070411, 81100334, 81100335, 81100336, 81100348, 81101869, and 81170515), National Science Fund for Distinguished Young Scholars (number 81125002), 973 Program (2009CB521904, 2011CB503906), Key Project of Chinese Ministry of Education (109097), Key Clinical Research Project of Public Health Ministry of China 2010–2012, Natural Science Foundation of Shandong Province (ZR2009CM001, ZR2010HQ002, ZR2010CQ040), National Key Clinical Specialist Vocational School about clinical speciality for blood disorders, Clinical Medicine Center Foundation of Shandong Province, Leading Medical Professionals Foundation of Shandong Province, Outstanding Young Scientist Research Award Foundation of Shandong Province (2009BSB01001, BS2009SW014, BS2010YY024, BS2010YY039, BS2011SW013, BS2011YY021), the Research Fund for the Doctoral Program of Higher Education of China (20100131120058), and the State Program of National Natural Science Foundation of China for Innovative Research Group 2011–2013 (81021001).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Hematology Oncology Centre, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China

    Shu-qian Xu, Chun-yan Wang, Xiao-juan Zhu, Xiao-yuan Dong, Yan Shi, Jun Peng, Ping Qin, Jian-zhi Sun & Ming Hou

  2. Department of General Medicine, Second Hospital of Shandong University, Jinan, China

    Chun-yan Wang

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

    Xiao-juan Zhu

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

    Jun Peng & Ming Hou

  5. Department of Hematology, Second Hospital of Shandong University, Jinan, China

    Chengshan Guo

  6. Canadian Blood Services and Toronto Platelet Immunobiology Group and Department of Laboratory Medicine and Pathobiology, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Heyu Ni

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  1. Shu-qian Xu
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  2. Chun-yan Wang
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  5. Yan Shi
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  8. Jian-zhi Sun
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  9. Chengshan Guo
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  11. Ming Hou
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Corresponding authors

Correspondence to Yan Shi or Ming Hou.

Additional information

Shu-qian Xu, Chun-yan Wang, and Xiao-juan Zhu contributed equally to this work.

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Supplementary Table 1

Clinical characteristics of ITP patients. (DOC 40 kb)

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Xu, Sq., Wang, Cy., Zhu, Xj. et al. Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia. Ann Hematol 91, 1623–1631 (2012). https://doi.org/10.1007/s00277-012-1451-0

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  • DOI: https://doi.org/10.1007/s00277-012-1451-0

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