title: IL-21 isoform is a membrane-bound ligand and activates directly interacted cells.
abstract: IL-21 is a pleiotropic cytokine that regulates the function of T cells, B cells, natural killer cells, and myeloid cells. We previously identified an IL-21 isoform, IL-21iso, in humans and mice, and found that IL-21iso was secreted in much smaller amounts than conventional IL-21. In this study, we determined that secreted IL-21iso also has less signaling activity than IL-21. However, the amounts of intracellular IL-21 or IL-21iso, and the level of STAT3 phosphorylation induced by the two IL-21 forms, were similar. IL-21-sensitive reporter cells co-cultured with cells producing IL-21iso showed STAT3 activation, apoptosis, and proliferation. However, when IL-21iso-producing cells were cultured in a transwell chamber, which prevented direct contact with the IL-21-sensitive cells, no IL-21iso-induced signaling was observed. Though IL-21iso is secreted in smaller amounts and has less potent signaling activity than IL-21, IL-21iso acts both on IL-21iso-bearing cells and other IL-21-sensitive cells through direct interactions probably without being secreted. Thus, IL-21iso's regulation of immune cells may be limited to the immediate proximity around the IL-21iso-producing cells, in regions such as immune organs or inflammation sites.
authors: Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors: Hidetoshi
authors: H
authors: Nara
authors: Mizanur
authors: M
authors: Rahman
authors: Akemi
authors: A
authors: Araki
authors: Lianjin
authors: L
authors: Jin
authors: Yuji
authors: Y
authors: Takeda
authors: Hironobu
authors: H
authors: Asao
mesh_terms: D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D015398:Signal Transduction; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D008024:Ligands; D020033:Protein Isoforms; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21