Skip to main content

Advertisement

Log in

IL-21 and IL-21 receptor

A new cytokine pathway modulates innate and adaptive immunity

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Interleukin (IL)-21 is a new member of the type I cytokine superfamily. Although it is most homologous to IL-15, it has a unique receptor chain, IL-21R, that pairs with the γ-common cytokine receptor chain. The first experiments examining the biology of the IL-21 pathway reveal that it is a cytokine with effects on natural killer (NK) cells, T cells, and B cells. Mice deficient in the IL-21 R have also been made, and are being examined for the effects of the IL-21/IL-21R pathway in vivo. Here we summarize our current knowledge of this new cytokine pathway, and its role in innate and adaptive immunity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bazan JF: Structural design and mole cular evolution of acytokine receptor superfamily. Proc Nat Acad Sci USA 1990;87:6934–6938.

    Article  PubMed  CAS  Google Scholar 

  2. Kasaian MT, Whitters MJ, Carter LL Lowe LD, Jussif JM, Deng B, 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 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ: Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Nat Acad Sci USA 2000;97:11439–11444.

    Article  PubMed  CAS  Google Scholar 

  5. Leonard WJ, O'Shea JJ: Jaks and STATs: biological implications. Ann Rev Immunol 1998;16:293–322.

    Article  CAS  Google Scholar 

  6. Parrish-Novak J, Foster DC, Holly RD, Clegg CH: Interleukin-21 and the IL-21 receptor novel effectors of NK and T cell responses. J Leukocyte Biol 2002;72: 856–863.

    PubMed  CAS  Google Scholar 

  7. Anderson DM, Johnson L, Glaccum MB, Copeland NG, Gilbert DJ, Jenkins NA, et al.: Chromosomal assignment and genomic structure of IL15. Genomics 1995;25: 701–706.

    Article  PubMed  CAS  Google Scholar 

  8. Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, Grusby MJ: Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically, inhibits the differentiation of naive Th cells into interferon gamma-producing Thl cells. J Exp Med 2002;196: 969–977.

    Article  PubMed  CAS  Google Scholar 

  9. Tagaya Y, Bamford RN, DeFilippis AP, Waldmann TA: IL-15: a pleiotropic cytokine with diverse recptor/signaling pathways whose expression is controlled at multiple levels. Immunity 1996;4:329–336.

    Article  PubMed  CAS  Google Scholar 

  10. Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K: cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J. Immunol 2001;167:1–5.

    PubMed  CAS  Google Scholar 

  11. Habib T, Senadheera S, Weinberg K, Kaushansky K: The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK 3. Biochemistry 2002;41:8725–8731.

    Article  PubMed  CAS  Google Scholar 

  12. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O: Signaling through the hematopoietic cytokine receptors. Ann Rev Immunol 1995;13:369–398.

    Article  CAS  Google Scholar 

  13. Strengell M, Sareneva T, Foster D, Julkunen I, Matikainen S: IL-21 Up-re gulates the expression of genesassociated with innate immunity and Th1 response. J Immunol 2002;169:3600–3605.

    PubMed  Google Scholar 

  14. Brenne AT, Baade Ro T, Waage A, Sundan A, Borset M, Hjorth-Hansen H: Interfleukin-21 is a growth and survival factor for human myeloma cells. Blood 2002;99: 3756–3762.

    Article  PubMed  CAS  Google Scholar 

  15. Suto A, Nakajima H, Hirose K, Suzuki K, Kagami SI, Seto Y, et al: Interleukin-21 prevents antigen-induced IgE production by inhibiting germline C ε transcription of IL-4-stimulated B cells. Blood 2002;100:4565–4573.

    Article  PubMed  CAS  Google Scholar 

  16. Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, et al: Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficientmice. J Exp Med 2000;191:771–780.

    Article  PubMed  CAS  Google Scholar 

  17. Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, et al.: Acritical role for IL-21 inregulating immuno globulin production. Science 2002;298:1630–1634.

    Article  PubMed  CAS  Google Scholar 

  18. Van Leeuwen EM, Gamadia LE, Baars PA, Remmerswaal EB, Ten Berge IJ, Van Lier RA: Proliferation requirements of cytomegalovirus- specific, effector-type human CD8(+) T cells. J Immunol 2002;169: 5838–5843.

    PubMed  Google Scholar 

  19. Kuhn R, Rajewsky K, Muller W: Generation and analysis of interleukin-4 deficient mice. Science 1991;254: 707–710.

    Article  PubMed  CAS  Google Scholar 

  20. Ueda C, Akasaka T, Kurata M, Maesako Y, Nishikori M, Ichinohasama R, et al.: The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma. Oncogene 2002:21:368–376.

    Article  PubMed  CAS  Google Scholar 

  21. Bennett F, Luxenberg D, Ling V, Wang I-M, Marquette K, Lowe D, et al.: PD-1 engagement upon TCR activitation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4 and IL-21, but not CD28, IL-7 and IL-15 responses. J. Immunol 2003; 170:711–718.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Collins, M., Whitters, M.J. & Young, D.A. IL-21 and IL-21 receptor. Immunol Res 28, 131–140 (2003). https://doi.org/10.1385/IR:28:2:131

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/IR:28:2:131

Key Words

Navigation