Interleukin-21, also alternatively named IL-17C, is a pro-inflammatory cytokine and member of the IL-17 family. The IL-17 family is comprised of at least six members: IL-17A-F (1, 2). Interleukin-21, along with IL-17B, appears to stimulate release of TNFa and IL-1b from the monocytic THP-1 line thus appearing to have a different receptor and induction pattern than IL-17A (1, 2). As a pro-inflammatory cytokine IL-21 augments the inflammatory process in arthritis models (2, 3). Interleukin-21 is induced in epithelial cells by bacterial antigens and other inflammatory ligands such as imiquimod, exhibiting a direct linkage with innate immune receptors such as TLRs (2, 3). The IL-21 receptor complex appears to be comprised of IL-17RA or IL-17RE. Antibody to IL-21 allows further analysis of the unique regulatory activity, cellular receptors and cellular targets of IL-21 (IL-17C) versus other members of the IL-17 family such as IL-17A. The study of Interleukin-21 and its contribution to diseases caused by impaired epithelial barriers in autoimmune and inflammatory diseases such as psoriasis, asthma or inflammatory bowel disease potentiate development of new therapies directed at regulation of IL-21 or other IL-17 family members (4). The linkage of IL-21 with epithelial cells also furthers the study of the innate immune functions of epithelial cells.
1. Ramirez-Carrozzi, V 2011 Nature Immunol doi: 10.1038/ni.258.
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5. John S. Yi, Jennifer T. Ingram, Allan J. Zajac. IL21-deficiency Influences CD8 T Cell Quality and Recall Responses Following an Acute Viral Infection. J Immunol. 2010 October 15; 185(8): 4835–4845.
6. Rosanne Spolski, Hyoung-Pyo Kim, Wei Zhu, David E. Levy, Warren J. Leonard. IL21 mediates suppressive effects via its induction of IL-10. J Immunol. 2009 March 1; 182(5): 2859–2867.
7. John S. Tzartos, Matthew J. Craner, Manuel A. Friese, Karen B. Jakobsen, Jia Newcombe, Margaret M. Esiri, Lars Fugger. IL21 and IL21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain. Am J Pathol. 2011 February; 178(2): 794–802.
8. James M Ertelt, Tanner M Johanns, Jared H Rowe, Sing Sing Way. Interleukin (IL)-21-independent pathogen-specific CD8+ Tcell expansion, and IL21-dependent suppression of CD4+ Tcell IL-17 production. Immunology. 2010 October; 131(2): 183–191.