title: Role of interleukin-21 isoform in dextran sulfate sodium (DSS)-induced colitis.
abstract: Interleukin-21 (IL-21) is overproduced in human intestines affected by inflammatory bowel disease (IBD) and in the gut of mice with DSS-induced colitis. IL-21-deficient mice are largely protected against DSS-induced colitis, indicating that IL-21 plays a key role in the development of IBD. We previously identified a novel IL-21 isoform named IL-21iso. In this study, we found that in addition to the conventional IL-21, IL-21iso mRNA was also expressed in the colon with DSS-induced colitis. To investigate whether IL-21iso plays a role in DSS-induced colitis, we established transgenic mice (mIL-21iso-Tg mice) that expressed mouse IL-21iso under the control of the lck proximal promoter. Although mIL-21iso-Tg mice did not have any gross physical abnormalities, their peripheral lymphocytes counts were higher than those in wild-type littermates. Notably, their CD8(+) T cell and CD4(+) effector memory T-cell populations were elevated. DSS-induced colitis was far more severe in the mIL-21iso-Tg mice than in wild-type mice, and was accompanied by a marked loss of body weight and by colon inflammation with increased cellular infiltration. In DSS-treated mice, colon tissues from mIL-21iso-Tg mice had significantly higher gene activation levels for cytokines such as IL-17A, TNF-α, IL-6, IL-10, and IL-4, and for transcription factors such as T-bet, GATA-3, RORγt, and Foxp3, than were found in wild-type mice. These results indicate that besides IL-21, IL-21iso may be another regulator of gut inflammation.
authors.affiliation: Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Araki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nara
authors.forename: Mizanur
authors.initials: M
authors.lastname: Rahman
authors.forename: Tadashi
authors.initials: T
authors.lastname: Onoda
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Farha Matin
authors.initials: FM
authors.lastname: Juliana
authors.forename: Lianjin
authors.initials: L
authors.lastname: Jin
authors.forename: Kazuko
authors.initials: K
authors.lastname: Murata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takeda
authors.forename: Hironobu
authors.initials: H
authors.lastname: Asao
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016264:Dextran Sulfate; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016264:Dextran Sulfate; D000098546:Interleukin-21