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Gene Review

IL21  -  interleukin 21

Homo sapiens

Synonyms: CVID11, IL-21, Interleukin-21, Za11
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Disease relevance of IL21


High impact information on IL21


Biological context of IL21

  • IL-21 signaling failed to stimulate CLL B-cell proliferation, but induced their apoptosis [7].
  • In this study, we have studied IL-15- and IL-21-induced gene expression in human primary NK and T cells and the NK-92 cell line [8].
  • IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response [8].
  • Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses [9].
  • Our data show that IL-21 modulates the phenotype of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands [10].

Anatomical context of IL21

  • AIM: To investigate whether IL21 controls MMP production by intestinal fibroblasts [11].
  • The potency of IL-21 was close to that of IL-6 in the OH-2 cell line [1].
  • We therefore examined whether IL-21 controls CD4(+)CD25(+) T cell function [12].
  • The biological role of IL-21 in the immune system is complex, as IL-21 has been shown to have the ability to both promote and inhibit immune responses [13].
  • Initial studies have demonstrated that IL-21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells [13].

Associations of IL21 with chemical compounds

  • The gamma(c) residues involved in IL-21 binding were defined by alanine-scanning mutational analysis [14].
  • In this study, we found that IL-21, in the presence of physiological concentration of hydrocortisone (HC), has a significant impact on the functions of NK cells derived from umbilical cord blood (CB) populations [15].
  • Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10 [16].
  • TCR-induced IL-21 gene expression was inhibited by cyclosporin A and FK506 [17].
  • An hIL-21 analog was designed to stabilize the region around helix C through the introduction of a segment grafted from hIL-4 [18].

Physical interactions of IL21

  • Although IL-21 binds to the IL-21R expressed on gamma(c)-deficient ED40515(-) cells, IL-21 is unable to transduce any intracytoplasmic signals [19].

Regulatory relationships of IL21


Other interactions of IL21


Analytical, diagnostic and therapeutic context of IL21


  1. Interleukin-21 is a growth and survival factor for human myeloma cells. Brenne, A.T., Ro, T.B., Waage, A., Sundan, A., Borset, M., Hjorth-Hansen, H. Blood (2002) [Pubmed]
  2. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Monteleone, G., Monteleone, I., Fina, D., Vavassori, P., Del Vecchio Blanco, G., Caruso, R., Tersigni, R., Alessandroni, L., Biancone, L., Naccari, G.C., MacDonald, T.T., Pallone, F. Gastroenterology (2005) [Pubmed]
  3. Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis. Jüngel, A., Distler, J.H., Kurowska-Stolarska, M., Seemayer, C.A., Seibl, R., Forster, A., Michel, B.A., Gay, R.E., Emmrich, F., Gay, S., Distler, O. Arthritis Rheum. (2004) [Pubmed]
  4. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. King, C., Ilic, A., Koelsch, K., Sarvetnick, N. Cell (2004) [Pubmed]
  5. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Parrish-Novak, J., Dillon, S.R., Nelson, A., Hammond, A., Sprecher, C., Gross, J.A., Johnston, J., Madden, K., Xu, W., West, J., Schrader, S., Burkhead, S., Heipel, M., Brandt, C., Kuijper, J.L., Kramer, J., Conklin, D., Presnell, S.R., Berry, J., Shiota, F., Bort, S., Hambly, K., Mudri, S., Clegg, C., Moore, M., Grant, F.J., Lofton-Day, C., Gilbert, T., Rayond, F., Ching, A., Yao, L., Smith, D., Webster, P., Whitmore, T., Maurer, M., Kaushansky, K., Holly, R.D., Foster, D. Nature (2000) [Pubmed]
  6. A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Caruso, R., Fina, D., Peluso, I., Stolfi, C., Fantini, M.C., Gioia, V., Caprioli, F., Del Vecchio Blanco, G., Paoluzi, O.A., Macdonald, T.T., Pallone, F., Monteleone, G. Gastroenterology (2007) [Pubmed]
  7. Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells. de Totero, D., Meazza, R., Zupo, S., Cutrona, G., Matis, S., Colombo, M., Balleari, E., Pierri, I., Fabbi, M., Capaia, M., Azzarone, B., Gobbi, M., Ferrarini, M., Ferrini, S. Blood (2006) [Pubmed]
  8. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. Strengell, M., Sareneva, T., Foster, D., Julkunen, I., Matikainen, S. J. Immunol. (2002) [Pubmed]
  9. Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses. Sivakumar, P.V., Foster, D.C., Clegg, C.H. Immunology (2004) [Pubmed]
  10. IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells. Alves, N.L., Arosa, F.A., van Lier, R.A. J. Immunol. (2005) [Pubmed]
  11. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21. Monteleone, G., Caruso, R., Fina, D., Peluso, I., Gioia, V., Stolfi, C., Fantini, M.C., Caprioli, F., Tersigni, R., Alessandroni, L., Macdonald, T.T., Pallone, F. Gut (2006) [Pubmed]
  12. IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T Lymphocytes. Peluso, I., Fantini, M.C., Fina, D., Caruso, R., Boirivant, M., Macdonald, T.T., Pallone, F., Monteleone, G. J. Immunol. (2007) [Pubmed]
  13. Biology of IL-21 and the IL-21 receptor. Mehta, D.S., Wurster, A.L., Grusby, M.J. Immunol. Rev. (2004) [Pubmed]
  14. Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain. Zhang, J.L., Foster, D., Sebald, W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  15. Effect of IL-21 on NK cells derived from different umbilical cord blood populations. Perez, S.A., Mahaira, L.G., Sotiropoulou, P.A., Gritzapis, A.D., Iliopoulou, E.G., Niarchos, D.K., Cacoullos, N.T., Kavalakis, Y.G., Antsaklis, A.I., Sotiriadou, N.N., Baxevanis, C.N., Papamichail, M. Int. Immunol. (2006) [Pubmed]
  16. Interleukin-21 inhibits dendritic cell activation and maturation. Brandt, K., Bulfone-Paus, S., Foster, D.C., Rückert, R. Blood (2003) [Pubmed]
  17. Calcium-dependent activation of interleukin-21 gene expression in T cells. Kim, H.P., Korn, L.L., Gamero, A.M., Leonard, W.J. J. Biol. Chem. (2005) [Pubmed]
  18. The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue. Bondensgaard, K., Breinholt, J., Madsen, D., Omkvist, D.H., Kang, L., Worsaae, A., Becker, P., Schiødt, C.B., Hjorth, S.A. J. Biol. Chem. (2007) [Pubmed]
  19. Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. Asao, H., Okuyama, C., Kumaki, S., Ishii, N., Tsuchiya, S., Foster, D., Sugamura, K. J. Immunol. (2001) [Pubmed]
  20. IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. Strengell, M., Julkunen, I., Matikainen, S. J. Leukoc. Biol. (2004) [Pubmed]
  21. IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells. Burgess, S.J., Marusina, A.I., Pathmanathan, I., Borrego, F., Coligan, J.E. J. Immunol. (2006) [Pubmed]
  22. Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis. Li, J., Shen, W., Kong, K., Liu, Z. Scand. J. Immunol. (2006) [Pubmed]
  23. IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells. Strengell, M., Matikainen, S., Sirén, J., Lehtonen, A., Foster, D., Julkunen, I., Sareneva, T. J. Immunol. (2003) [Pubmed]
  24. Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis. Distler, J.H., Jüngel, A., Kowal-Bielecka, O., Michel, B.A., Gay, R.E., Sprott, H., Matucci-Cerinic, M., Chilla, M., Reich, K., Kalden, J.R., Müller-Ladner, U., Lorenz, H.M., Gay, S., Distler, O. Arthritis Rheum. (2005) [Pubmed]
  25. Expression of functional interleukin-21 receptor on adult T-cell leukaemia cells. Ueda, M., Imada, K., Imura, A., Koga, H., Hishizawa, M., Uchiyama, T. Br. J. Haematol. (2005) [Pubmed]
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