Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Impaired glucocorticoid receptor expression and mitochondrial metabolism in MDSCs contribute to glucocorticoid resistance in immune thrombocytopenia

Cellular & Molecular Immunology volume 19, pages 858–860 (2022)Cite this article

Subjects

In this issue of Cellular & Molecular Immunology, Hou and coworkers provide novel insights into glucocorticoid (GC) treatment refractoriness in immune thrombocytopenia (ITP), reporting that myeloid-derived suppressor cells (MDSCs) contribute to GC resistance in ITP via impairments in their glucocorticoid receptor (GR) expression and mitochondrial metabolism [1].

ITP is an autoimmune bleeding disorder characterized by platelet destruction and impaired platelet production resulting in platelet counts of less than 100 × 109/L [2, 3]. Clinical symptoms include petechiae, purpura, mucosal bleeding, and, in rare cases, intracranial hemorrhage, and patients frequently experience a reduced health-related quality of life [4]. The pathophysiology of ITP is complex and multifactorial, involving various cell types [4]. Strikingly, there is a loss of immune tolerance that involves quantitative and qualitative dysregulation of CD4+ T regulatory cells (Tregs), which enhances the initiation and perpetuation of ITP [2]. In addition, dendritic cells and MDSCs have been shown to be impaired in ITP [2, 5]. Though the mechanisms are incompletely understood, the loss of immune tolerance culminates in peripheral platelet destruction due to platelet-specific autoantibodies and/or CD8+ cytotoxic T cells or bone marrow megakaryocyte impairment resulting in decreased platelet production [4].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Hou Y, Xie J, Wang S, Li D, Wang L, Wang H, et al. Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia. Cell Mol Immunol. 2022;19:764–76.

    Google Scholar 

  2. Semple JW, Rebetz J, Maouia A, Kapur R. An update on the pathophysiology of immune thrombocytopenia. Curr Opin Hematol. 2020;27:423–29. Epub 2020/09/02.

    CAS  PubMed  Google Scholar 

  3. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93. Epub 2008/11/14.

    Article  CAS  Google Scholar 

  4. Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6:16. Epub 2017/02/18.

    Article  Google Scholar 

  5. Hou Y, Feng Q, Xu M, Li GS, Liu XN, Sheng Z, et al. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood. 2016;127:1587–97. Epub 2016/01/09.

    Article  CAS  Google Scholar 

  6. Miltiadous O, Hou M, Bussel JB. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood. 2020;135:472–90. Epub 2019/11/23.

    Article  Google Scholar 

  7. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3:3829–66. Epub 2019/12/04.

    Article  CAS  Google Scholar 

  8. Lu Y, Cheng L, Li F, Ji L, Shao X, Wu B, et al. The abnormal function of CD39(+) regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia. Ann Hematol. 2019;98:1845–54. Epub 2019/06/04.

    Article  CAS  Google Scholar 

  9. Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome. Eur J Haematol. 2007;79:310–6. Epub 2007/08/19.

    Article  CAS  Google Scholar 

  10. Williams EL, Stimpson ML, Lait PJP, Schewitz-Bowers LP, Jones LV, Dhanda AD, et al. Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14(++) CD16(+) intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype. Br J Haematol. 2021;192:375–84. Epub 2020/12/19.

    Article  CAS  Google Scholar 

  11. Kapur R, Heitink-Polle KM, Porcelijn L, Bentlage AE, Bruin MC, Visser R, et al. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia. Blood. 2015;125:1793–802. Epub 2014/12/31.

    Article  CAS  Google Scholar 

  12. Guo L, Kapur R, Aslam R, Hunt K, Hou Y, Zufferey A, et al. Antiplatelet antibody-induced thrombocytopenia does not correlate with megakaryocyte abnormalities in murine immune thrombocytopenia. Scand J Immunol. 2018;88:e12678. Epub 2018/06/02.

    Article  CAS  Google Scholar 

  13. Chow L, Aslam R, Speck ER, Kim M, Cridland N, Webster ML, et al. A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood. 2010;115:1247–53. Epub 2009/12/17.

    Article  CAS  Google Scholar 

  14. Kapur R, Aslam R, Speck ER, Rebetz JM, Semple JW. Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). Platelets. 2020;31:399–402. Epub 2019/05/31.

    Article  CAS  Google Scholar 

  15. Jolink AC, Nelson VS, Schipperus MR, Amini SN, Vidarsson G, van der Schoot CE, et al. Potential Diagnostic Approaches for Prediction of Therapeutic Responses in Immune Thrombocytopenia. J Clin Med. 2021;10:3403. Epub 2021/08/08.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sanquin Research, Department of Experimental Immunohematology, Amsterdam and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Rick Kapur

Authors
  1. Rick Kapur
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rick Kapur.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kapur, R. Impaired glucocorticoid receptor expression and mitochondrial metabolism in MDSCs contribute to glucocorticoid resistance in immune thrombocytopenia. Cell Mol Immunol 19, 858–860 (2022). https://doi.org/10.1038/s41423-022-00880-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-022-00880-3

Search

Advanced search

Quick links