The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2 (IL2), interleukin 7 (IL7) and interleukin 15 (IL15). This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants encoding the same protein have been described.
Parrish-Novak J, Dillon SR, Nelson A, et al. (2000). "Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function". Nature. 408 (6808): 57–63. doi:10.1038/35040504. PMID11081504.
Asao H, Okuyama C, Kumaki S, et al. (2001). "Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex". J. Immunol. 167 (1): 1–5. doi:10.4049/jimmunol.167.1.1. PMID11418623.
Jüngel A, Distler JH, Kurowska-Stolarska M, et al. (2004). "Expression of interleukin-21 receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis". Arthritis Rheum. 50 (5): 1468–1476. doi:10.1002/art.20218. PMID15146416.
Distler JH, Jüngel A, Kowal-Bielecka O, et al. (2005). "Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis". Arthritis Rheum. 52 (3): 856–864. doi:10.1002/art.20883. PMID15751077.
de Totero D, Meazza R, Zupo S, et al. (2006). "Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells". Blood. 107 (9): 3708–3715. doi:10.1182/blood-2005-09-3535. PMID16391014.
Pène J, Guglielmi L, Gauchat JF, et al. (2007). "IFN-gamma-mediated inhibition of human IgE synthesis by IL-21 is associated with a polymorphism in the IL-21R gene". J. Immunol. 177 (8): 5006–13. doi:10.4049/jimmunol.177.8.5006. PMID17015683.
Asano K, Ikegami H, Fujisawa T, et al. (2007). "Molecular scanning of interleukin-21 gene and genetic susceptibility to type 1 diabetes". Hum. Immunol. 68 (5): 384–391. doi:10.1016/j.humimm.2007.01.009. PMID17462506.
Akamatsu N, Yamada Y, Hasegawa H, et al. (2007). "High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma". Cancer Lett. 256 (2): 196–206. doi:10.1016/j.canlet.2007.06.001. PMID17624663.