Interleukin-21 signaling: functions in cancer and autoimmunity
- PMID: 18056166
- DOI: 10.1158/1078-0432.CCR-07-1238
Interleukin-21 signaling: functions in cancer and autoimmunity
Abstract
Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15, yet possesses several biological properties distinct from these cytokines. IL-21 is produced mainly by activated CD4(+) T cells and natural killer T cells and mediates its activity by binding to the IL-21 receptor (IL-21R), consisting of an IL-21-specific alpha chain (IL-21Ralpha; JAK/STAT) that heterodimerizes with the common gamma chain (CD132). Intracellular signaling occurs through the Janus-activated kinase/signal transducer and activator of transcription pathways. Physiologic expression of IL-21R is restricted to lymphoid tissues and peripheral blood mononuclear cells; however, other tissues such as epithelium, synovium, or transformed cells can acquire expression of both components of IL-21R heterodimer. IL-21 has complex activities on a wide variety of cell types, leading to enhancement of adaptive T-cell immunity, antibody production, activation of natural killer cell subtypes, and opposition to suppressive effects mediated by regulatory T cells. Functionally, these activities promote immune responses and point to a physiologic role of IL-21 in autoimmunity and immune enhancement. Therapeutic manipulation of IL-21 activity may allow improved immunotherapy for cancer as well as insights into autoimmune disease. Recently conducted phase 1 trials in metastatic melanoma and renal cell carcinoma have shown that recombinant IL-21 has a favorable safety profile and support its continued investigation as a potential anticancer drug.
Similar articles
-
IL-21: a novel IL-2-family lymphokine that modulates B, T, and natural killer cell responses.J Allergy Clin Immunol. 2003 Dec;112(6):1033-45. doi: 10.1016/j.jaci.2003.08.039. J Allergy Clin Immunol. 2003. PMID: 14657853 Review.
-
Interleukin-21: a new modulator of immunity, infection, and cancer.Cytokine Growth Factor Rev. 2007 Jun-Aug;18(3-4):223-32. doi: 10.1016/j.cytogfr.2007.04.003. Epub 2007 May 16. Cytokine Growth Factor Rev. 2007. PMID: 17509926 Review.
-
IL-21: roles in immunopathology and cancer therapy.Tissue Antigens. 2009 Dec;74(6):467-79. doi: 10.1111/j.1399-0039.2009.01382.x. Epub 2009 Oct 21. Tissue Antigens. 2009. PMID: 19845910 Review.
-
Endogenous IL-21 restricts CD8+ T cell expansion and is not required for tumor immunity.J Immunol. 2009 Dec 1;183(11):7326-36. doi: 10.4049/jimmunol.0902697. Epub 2009 Nov 13. J Immunol. 2009. PMID: 19915059
-
A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.J Immunol. 2009 Apr 15;182(8):4649-56. doi: 10.4049/jimmunol.0804350. J Immunol. 2009. PMID: 19342640
Cited by
-
Combination strategies to enhance antitumor ADCC.Immunotherapy. 2012 May;4(5):511-27. doi: 10.2217/imt.12.38. Immunotherapy. 2012. PMID: 22642334 Free PMC article. Review.
-
TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity.Sci Adv. 2021 Sep 17;7(38):eabi6515. doi: 10.1126/sciadv.abi6515. Epub 2021 Sep 15. Sci Adv. 2021. PMID: 34524845 Free PMC article.
-
An updated profile of the bovine acute phase response following an intravenous lipopolysaccharide challenge.J Anim Sci. 2023 Jan 3;101:skad133. doi: 10.1093/jas/skad133. J Anim Sci. 2023. PMID: 37115605 Free PMC article.
-
Targeting interleukin-21 in rheumatoid arthritis.Mol Biol Rep. 2011 Mar;38(3):1717-21. doi: 10.1007/s11033-010-0285-x. Epub 2010 Sep 17. Mol Biol Rep. 2011. PMID: 20848219 Review.
-
Association between IL-21 gene rs907715 polymorphisms and Graves' disease in a Southern Chinese population.Exp Ther Med. 2014 Jul;8(1):213-218. doi: 10.3892/etm.2014.1707. Epub 2014 May 12. Exp Ther Med. 2014. PMID: 24944624 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials