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Erschienen in: Journal of Clinical Immunology 2/2010

01.03.2010

Elevated Interleukin-21 Correlated to Th17 and Th1 Cells in Patients with Immune Thrombocytopenia

verfasst von: Xiaojuan Zhu, Daoxin Ma, Jingbo Zhang, Jun Peng, Xun Qu, Chunyan Ji, Ming Hou

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2010

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Abstract

Background

Interleukin-21 (IL-21) is critical in the development of autoimmune diseases. The role of IL-21 in the pathogenesis of immune thrombocytopenia (ITP) remains unknown.

Materials and Methods

We examined the expression of IL-21, IL-17, and interferon (IFN)-γ in ITP patients and controls by enzyme-linked immunosorbent assay and flow cytometry. Detection of specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies was measured by modified monoclonal antibody specific immobilization of platelet antigens.

Results

IL-21 was expressed on both CD3+CD8 T cells and CD3+CD8+ T cells by flow cytometry. Plasma IL-21 level and the percentage of CD3+CD8IL-21+ T cells and CD3+CD8+IL-21+ T cells were significantly elevated in ITP patients compared to controls. The percentage of CD3+CD8IL-17+ T (Th17), CD3+CD8IFN-γ+ T (Th1), and CD3+CD8+IFN-γ+ T (Tc1) cells also significantly increased in ITP patients. Moreover, we found a significant positive correlation between CD3+CD8IL-21+ T cells and Th17 cells. In addition, a positive correlation between CD3+CD8IL-21+ T cells and Th1 cells was also found.

Conclusion

Together, our results indicated a possible role of IL-21 in ITP patients correlated to Th17 and Th1 cells, and blockade of IL-21 may be a reasonable therapeutic strategy for ITP especially those with active disease.
Literatur
1.
Zurück zum Zitat Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008;99:4–13.PubMed Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008;99:4–13.PubMed
2.
Zurück zum Zitat Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1⁄Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71:283–8.CrossRefPubMed Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1⁄Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71:283–8.CrossRefPubMed
3.
Zurück zum Zitat Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2004;103:2645–7.CrossRefPubMed Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2004;103:2645–7.CrossRefPubMed
4.
Zurück zum Zitat Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, et al. Abnormality of CD4(+)CD25(+) regulatory T cell in idiopathic thrombocytopenic purpura. Eur J Haematol. 2007;78:139–43.PubMed Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, et al. Abnormality of CD4(+)CD25(+) regulatory T cell in idiopathic thrombocytopenic purpura. Eur J Haematol. 2007;78:139–43.PubMed
5.
Zurück zum Zitat Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood. 2008;112:1325–8.CrossRefPubMed Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood. 2008;112:1325–8.CrossRefPubMed
6.
Zurück zum Zitat Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123–4.CrossRefPubMed Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123–4.CrossRefPubMed
7.
Zurück zum Zitat Zhao C, Li X, Zhang F, Wang L, Peng J, Hou M. Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies. Haematologica. 2008;93:1428–30.PubMed Zhao C, Li X, Zhang F, Wang L, Peng J, Hou M. Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies. Haematologica. 2008;93:1428–30.PubMed
8.
Zurück zum Zitat Spolski R, Leonard WL. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 2007;26:57–79.CrossRef Spolski R, Leonard WL. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 2007;26:57–79.CrossRef
9.
Zurück zum Zitat Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63.CrossRefPubMed Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63.CrossRefPubMed
10.
Zurück zum Zitat Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, Sivakumar PV. Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 2007;13:6926–32.CrossRefPubMed Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, Sivakumar PV. Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 2007;13:6926–32.CrossRefPubMed
11.
Zurück zum Zitat Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, et al. Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum. 2007;56:1152–63.CrossRefPubMed Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, et al. Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum. 2007;56:1152–63.CrossRefPubMed
12.
Zurück zum Zitat Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R:Fc reduces disease progression. J Immunol. 2007;178:3822–30.PubMed Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R:Fc reduces disease progression. J Immunol. 2007;178:3822–30.PubMed
13.
Zurück zum Zitat Fina D, Sarra M, Fantini MC, Rizzo A, Caruso R, Caprioli F, et al. Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology. 2008;134:1038–48.CrossRefPubMed Fina D, Sarra M, Fantini MC, Rizzo A, Caruso R, Caprioli F, et al. Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology. 2008;134:1038–48.CrossRefPubMed
14.
Zurück zum Zitat Mitoma H, Horiuchi T, Kimoto Y, Tsukamoto H, Uchino A, Tamimoto Y, et al. Decreased expression of interleukin-21 receptor on peripheral B lymphocytes in systemic lupus erythematosus. Int J Mol Med. 2005;16:609–15.PubMed Mitoma H, Horiuchi T, Kimoto Y, Tsukamoto H, Uchino A, Tamimoto Y, et al. Decreased expression of interleukin-21 receptor on peripheral B lymphocytes in systemic lupus erythematosus. Int J Mol Med. 2005;16:609–15.PubMed
15.
Zurück zum Zitat Andersson AK, Feldmann M, Brennan FM. Neutralizing IL-21 and IL-15 inhibits pro-inflammatory cytokine production in rheumatoid arthritis. Scand Immunol. 2008;68:103–11.CrossRef Andersson AK, Feldmann M, Brennan FM. Neutralizing IL-21 and IL-15 inhibits pro-inflammatory cytokine production in rheumatoid arthritis. Scand Immunol. 2008;68:103–11.CrossRef
16.
Zurück zum Zitat Distler JH, Jüngel A, Kowal-Bielecka O, Michel BA, Gay RE, Sprott H, et al. Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis. Arthritis Rheum. 2005;52:856–64.CrossRefPubMed Distler JH, Jüngel A, Kowal-Bielecka O, Michel BA, Gay RE, Sprott H, et al. Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis. Arthritis Rheum. 2005;52:856–64.CrossRefPubMed
17.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
18.
Zurück zum Zitat Hou M, Peng J, Shi Y, Zhang C, Qin P, Zhao C, et al. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;70:353–7.CrossRefPubMed Hou M, Peng J, Shi Y, Zhang C, Qin P, Zhao C, et al. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;70:353–7.CrossRefPubMed
19.
Zurück zum Zitat Spolski R, Leonard WJ. The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer. Curr Opin Immunol. 2008;20:295–301.CrossRefPubMed Spolski R, Leonard WJ. The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer. Curr Opin Immunol. 2008;20:295–301.CrossRefPubMed
20.
Zurück zum Zitat Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 2007;448:480–3.CrossRefPubMed Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 2007;448:480–3.CrossRefPubMed
21.
Zurück zum Zitat Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484–7.CrossRefPubMed Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484–7.CrossRefPubMed
22.
Zurück zum Zitat Fina D. Role of interleukin-21 in inflammation and allergy. Inflamm Allergy Drug Targets. 2007;6:63–8.CrossRefPubMed Fina D. Role of interleukin-21 in inflammation and allergy. Inflamm Allergy Drug Targets. 2007;6:63–8.CrossRefPubMed
23.
Zurück zum Zitat Strengel M, Sareneva T, Foste D, Julkunen I, Matikainen S. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 responses. J Immunol. 2002;169:3600–5. Strengel M, Sareneva T, Foste D, Julkunen I, Matikainen S. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 responses. J Immunol. 2002;169:3600–5.
24.
Zurück zum Zitat Monteleone G, Monteleone I, Fina D, Vavassori P, Del Vecchio Blanco G, Caruso R, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology. 2005;128:687–94.CrossRefPubMed Monteleone G, Monteleone I, Fina D, Vavassori P, Del Vecchio Blanco G, Caruso R, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology. 2005;128:687–94.CrossRefPubMed
25.
Zurück zum Zitat Fina D, Sarra M, Caruso R, Del Vecchio Blanco G, Pallone F, MacDonald T, et al. Interleukin-21 contributes to the mucosal T helper Cell type 1 response in celiac disease. Gut. 2008;57:887–92.CrossRefPubMed Fina D, Sarra M, Caruso R, Del Vecchio Blanco G, Pallone F, MacDonald T, et al. Interleukin-21 contributes to the mucosal T helper Cell type 1 response in celiac disease. Gut. 2008;57:887–92.CrossRefPubMed
26.
Zurück zum Zitat Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, et al. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon g-producing Th1 cells. J Exp Med. 2002;196:969–77.CrossRefPubMed Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, et al. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon g-producing Th1 cells. J Exp Med. 2002;196:969–77.CrossRefPubMed
27.
Zurück zum Zitat Fröhlich A, Marsland BJ, Sonderegger I, Kurrer M, Hodge MR, Harris NL. IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. Blood. 2007;109:2023–31.CrossRefPubMed Fröhlich A, Marsland BJ, Sonderegger I, Kurrer M, Hodge MR, Harris NL. IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. Blood. 2007;109:2023–31.CrossRefPubMed
28.
Zurück zum Zitat Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.CrossRefPubMed Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.CrossRefPubMed
29.
Zurück zum Zitat Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833–8.CrossRefPubMed Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833–8.CrossRefPubMed
30.
Zurück zum Zitat Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI. Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008;180:7097–101.PubMed Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI. Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008;180:7097–101.PubMed
Metadaten
Titel
Elevated Interleukin-21 Correlated to Th17 and Th1 Cells in Patients with Immune Thrombocytopenia
verfasst von
Xiaojuan Zhu
Daoxin Ma
Jingbo Zhang
Jun Peng
Xun Qu
Chunyan Ji
Ming Hou
Publikationsdatum
01.03.2010
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 2/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9353-1

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