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TRAIL in CD8+ T cells from patients with severe aplastic anemia

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Abstract

Severe aplastic anemia (SAA) is an autoimmune disease caused mainly by activated T lymphocytes. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of TNF family, which can induce apoptosis and play a significant role in the pathogenesis of many autoimmune disorders. In this study, we sought to investigate the role of TRAIL in peripheral CD8+ T cells (CTLs) from SAA patients to clarify the autoimmune mechanisms of bone marrow failure in SAA. The expression of TRAIL and TRAIL-R2 in CTLs from SAA patients and normal controls were determined by flow cytometry, real-time PCR, and western blot. Expression of perforin and granzyme B and apoptosis in CTLs were evaluated by flow cytometry. The expression of TRAIL and TRAIL-R2 in SAA patients was significantly decreased compared with controls; however, there was no statistical difference in TRAIL mRNA expression between the two groups. TRAIL expression in CTLs was negatively correlated with the expression of perforin and granzyme B, and negatively correlated with CTLs apoptosis in SAA patients. The TRAIL pathway may be responsible for abnormal CTL activation in SAA patients. Further study of TRAIL and its receptors may elucidate the pathogenesis of SAA.

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References

  1. Yamazaki H. Acquired aplastic anemia. Rinsho Ketsueki. 2016;57(2):91–7.

    PubMed  Google Scholar 

  2. Zeng Y, Katsanis E. The complex pathophysiology of acquired aplastic anaemia. Clin Exp Immunol. 2015;180(3):361–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Miano M, Dufour C. The diagnosis and treatment of aplastic anemia: a review. Int J Hematol. 2015;101(6):527–35.

    Article  CAS  PubMed  Google Scholar 

  4. Zonghong S, Meifeng T, Huaquan W, Limin X, Jun W, Rong F, et al. Circulating myeloid dendritic cells are increased in individuals with severe aplastic anemia. Int J Hematol. 2011;93(2):156–62.

    Article  PubMed  Google Scholar 

  5. Liu C, Sheng W, Fu R, Wang H, Li L, Liu H, et al. Differential expression of the proteome of myeloid dendritic cells in severe aplastic anemia. Cell Immunol. 2013;285(1–2):141–8.

    Article  CAS  PubMed  Google Scholar 

  6. Xing L, Liu C, Fu R, Wang H, Wang J, Liu X, et al. CD8+HLA-DR+ T cells are increased in patients with severe aplastic anemia. Mol Med Rep. 2014;10(3):1252–8.

    Article  CAS  PubMed  Google Scholar 

  7. Schrezenmeier H, Körper S, Höchsmann B. Aplastic anemia. Dtsch Med Wochenschr. 2014;139(49):2503–6.

    Article  CAS  PubMed  Google Scholar 

  8. Fulda S. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Adv Exp Med Biol. 2014;818:167–80.

    Article  CAS  PubMed  Google Scholar 

  9. Bertsch U, Röder C, Kalthoff H, Trauzold A. Compartmentalization of TNF-related apoptosis-inducing ligand(TRAIL) death receptor functions: emerging role of nuclear TRAIL-R2. Cell Death Dis. 2014;28(5):e1390.

    Article  Google Scholar 

  10. Allen JE, El-Deiry WS. Regulation of the human TRAIL gene. Cancer Biol Ther. 2012;13(12):1143–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bisgin A, Terzioglu E, Aydin C, Yoldas B, Yazisiz V, Balci N, et al. TRAIL death receptor-4, decoy receptor-1 and decoy receptor-2 expression on CD8+ T cells correlate with the disease severity in patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2010;11:192.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bossi F, Bernardi S, Zauli G, Secchiero P, Fabris B. TRAIL modulates the immune system and protects against the development of diabetes. J Immunol Res. 2015;2015:680749.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Xiao H, Wang S, Miao R, Kan W. TRAIL is associated with impaired regulation of CD4+CD25− T cells by regulatory T cells in patients with rheumatoid arthritis. J Clin Immunol. 2011;31:1112–9.

    Article  CAS  PubMed  Google Scholar 

  14. Gidvani V, Ramkissoon S, Sloand EM, Young NS. Cytokine gene polymorphisms in acquired bone marrow failure. Am J Hematol. 2007;82(8):721–4.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu F, Qiao J, Zhong XM, Wu QY, Chen W, Yao Y, et al. Antithymocyte globulin combined with cyclosporine A down-regulates T helper 1 cells by modulating T cell immune response cDNA 7 in aplastic anemia. Med Oncol. 2015;32(7):197.

    Article  PubMed  Google Scholar 

  16. Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V, et al. Deficient CD4+CD25+FOXP3+ T regulatory cells in acquired aplastic anemia. Blood. 2007;110(5):1603–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lehnert C, Weiswange M, Jeremias I, Bayer C, Grunert M, Debatin KM, et al. TRAIL-receptor costimulation inhibits proximal TCR signaling and suppresses human T cell activation and proliferation. J Immunol. 2014;193(8):4021–31.

    Article  CAS  PubMed  Google Scholar 

  18. Mezosi E, Wang SH, Utsugi S, Bajnok L, Bretz JD, Gauger PG, et al. Interleukin-1beta and tumor necrosis factor (TNF)-alpha sensitize human thyroid epithelial cells to TNF-related apoptosis-inducing ligand-induced apoptosis through increases in procaspase-7 and bid, and the down-regulation of p44/42 mitogen-activated protein kinase activity. J Clin Endocrinol Metab. 2004;89(1):250–7.

    Article  CAS  PubMed  Google Scholar 

  19. Inoue N, Watanabe M, Ishido N, Kodu A, Maruoka H, Katsumata Y, et al. Involvement of genes encoding apoptosis regulatory factors (FAS, FASL, TRAIL, BCL2, TNFR1 and TNFR2) in the pathogenesis of autoimmune thyroid diseases. Hum Immunol. 2016;77(10):944–51.

    Article  CAS  PubMed  Google Scholar 

  20. Lamhamedi-Cherradi SE, Zheng S, Tisch RM, Chen YH. Critical roles of tumor necrosis factor-related apoptosis-inducing ligand in type 1 diabetes. Diabetes. 2003;52(9):2274–8.

    Article  CAS  PubMed  Google Scholar 

  21. Audo R, Daien C, Papon L, Lukas C, Vittecoq O, Hahne M, et al. Osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as prognostic factors in rheumatoid arthritis: results from the ESPOIR cohort. Arthritis Res Ther. 2015;29(17):193.

    Article  Google Scholar 

  22. Tawdy MH, Abd El Nasser MM, Abd El Shafy SS, Nada MA, El Sirafy MN, Magd AH. Role of serum TRAIL level and TRAIL apoptosis gene expression in multiple sclerosis and relation to brain atrophy. J Clin Neurosci. 2014;21(9):1606–11.

    Article  CAS  PubMed  Google Scholar 

  23. Pundt N, Peters MA, Wunrau C, Strietholt S, Fehrmann C, Neugebauer K, et al. Susceptibility of rheumatoid arthritis synovial fibroblasts to FasL- and TRAIL-induced apoptosis is cell cycle-dependent. Arthritis Res Ther. 2009;11(1):R16.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Song K, Chen Y, Göke R, Wilmen A, Seidel C, Göke A, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression. J Exp Med. 2000;191(7):1095–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014;123(12):1818–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81570106, 81570111, 81400085, and 81400088), Tianjin Municipal Natural Science Foundation (14JCYBJC25400, 5JCYBJC24300, and 12JCZDJC21500), and Tianjin Science and Technology support key project plan (20140109).

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Author notes

  1. Chunyan Liu, Mengying Zheng, and Tian Zhang were contributed equally to this work.

Authors and Affiliations

  1. The Department of Hematology, General Hospital of Tianjin Medical University, 154 Anshandao, Heping District, Tianjin, 300052, China

    Chunyan Liu, Mengying Zheng, Tian Zhang, Rong Fu, Huaquan Wang, Ting Wang, Weiwei Qi & Zonghong Shao

  2. The Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin, China

    Zonghong Shao

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  1. Chunyan Liu
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  2. Mengying Zheng
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  3. Tian Zhang
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  4. Rong Fu
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  5. Huaquan Wang
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  6. Ting Wang
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  7. Weiwei Qi
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  8. Zonghong Shao
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Correspondence to Zonghong Shao.

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Liu, C., Zheng, M., Zhang, T. et al. TRAIL in CD8+ T cells from patients with severe aplastic anemia. Int J Hematol 106, 490–499 (2017). https://doi.org/10.1007/s12185-017-2279-0

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  • DOI: https://doi.org/10.1007/s12185-017-2279-0

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