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Overexpression of Interleukin 21 Induces Expansion of Hematopoietic Progenitor Cells

Abstract

The interleukin 21 (IL-21) receptor is expressed on T-cells, B-cells, and natural killer cells, and IL-21 is critical for regulating immunoglobulin production in vivo in cooperation with IL-4. So far, however, little is known about a role for IL-21 outside the immune system. We investigated the effect of IL-21 on hematopoiesis in vivo by using the hydrodynamics gene-delivery method. Overexpression of IL-21 increases Sca-1+ cells in the periphery and spleen. It also increases the numbers of c-Kit+, Sca-1+, and lineage-/low (KSL) cells and colony-forming units—granulocyte-macrophage (CFU-GM) in the spleen, indicating the expansion of hematopoietic progenitor cells. We found that even in RAG2-/- mice, which lack mature T-cells and B-cells, IL-21 induced an increase in KSL cells and CFU-GM in the spleen. These results demonstrate that IL-21 can induce the expansion of hematopoietic progenitor cells in vivo, even in the absence of mature T-cells and B-cells.

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References

  1. Parrish-Novak J, Dillon SR, Nelson A, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63.

    Article  PubMed  CAS  Google Scholar 

  2. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ. Cloning of a type I cytokine receptor most related to the IL-2 receptor βchain. Proc Natl Acad Sci U S A. 2000;97:11439- 11444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Asao H, Okuyama C, Kumaki S, et al. Cutting edge: the common γ-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol. 2001;167:1–5.

    Article  PubMed  CAS  Google Scholar 

  4. Habib T, Senadheera S, Weinberg K, Kaushansky K. The common 7 chain (γc) is a required signaling component of the IL- 21 recep- tor and supports IL-21-induced cell proliferation via JAK3. Biochemistry. 2002;41:8725–8731.

    Article  PubMed  CAS  Google Scholar 

  5. Kasaian MT, Whitters MJ, Carter LL, et al. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity. 2002;16:559–569.

    Article  PubMed  CAS  Google Scholar 

  6. Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002;298:1630- 1634.

    Article  CAS  PubMed  Google Scholar 

  7. Ozaki K, Spolski R, Ettinger R, et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol. 2004;173:5361–5371.

    Article  PubMed  CAS  Google Scholar 

  8. Wang G, Tschoi M, Spolski R, et al. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res. 2003;63: 9016–9022.

    PubMed  CAS  Google Scholar 

  9. Kishida T,Asada H, Itokawa Y, et al. Interleukin (IL)-21 and IL- 15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma. Mol Ther. 2003;8:552–558.

    Article  PubMed  CAS  Google Scholar 

  10. Zeng R, Spolski R, Finkelstein SE, et al. Synergy of IL-21 and IL-15 in regulating CD8+ T-cell expansion and function. J Exp Med. 2005;201:139–148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. King C, Ilic A, Koelsch K, Sarvetnick N. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 2004;117:265–277.

    Article  PubMed  CAS  Google Scholar 

  12. Nakauchi H, Takano H, Ema H, Osawa M. Further characterization of CD34-low/negative mouse hematopoietic stem cells. Ann N Y Acad Sci. 1999;872:57–66.

    Article  PubMed  CAS  Google Scholar 

  13. Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther. 1999;6: 1258–1266.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang G, Budker V, Wolff JA. High levels of foreign gene expres- sion in hepatocytes after tail vein injections of naked plasmid DNA. Hum Gene Ther. 1999;10:1735–1737.

    Article  PubMed  CAS  Google Scholar 

  15. Takakura N,Watanabe T, Suenobu S, et al. A role for hematopoietic stem cells in promoting angiogenesis. Cell. 2000;102:199–209.

    Article  PubMed  CAS  Google Scholar 

  16. Peters M, Schirmacher P, Goldschmitt J, et al. Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6- sIL-6R double transgenic mice. J Exp Med. 1997;185:755–766.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Terskikh AV, Miyamoto T, Chang C, et al. Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood. 2003;102:94–101.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Katsutoshi Ozaki.

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Ozaki, K., Hishiya, A., Hatanaka, K. et al. Overexpression of Interleukin 21 Induces Expansion of Hematopoietic Progenitor Cells. Int J Hematol 84, 224–230 (2006). https://doi.org/10.1532/IJH97.06036

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  • DOI: https://doi.org/10.1532/IJH97.06036

Key words

  • Interleukin 21
  • Hematopoietic progenitor cells
  • Overexpression
  • Expansion
  • CFU-GM