title: Interleukin-21 suppresses the differentiation and functions of T helper 2 cells.
abstract: T helper type 2 (Th2) cells, which produce interleukin-4 (IL-4), IL-5 and IL-13, control immunity to all forms of allergic inflammatory responses. Interleukin-21 (IL-21) reduces allergic symptoms in murine models and inhibits IL-4-induced IgE secretion by B cells. However, whether or not IL-21 directly affects Th2 cells, which leads to reduced allergic symptoms, is unclear. In this study, we investigated the effects of IL-21 on the differentiation and effector functions of Th2 cells. We found that IL-21 reduced the number of differentiated Th2 cells and these Th2 cells showed a diminished Th2 cytokine production. Interleukin-21 suppressed Th2 cytokine production of already polarized Th2 cells by down-regulation of transcription factor GATA-3. It also induced apoptosis of Th2 cells with decreased anti-apoptotic factor Bcl-2. Intranasal administration of IL-21 at the beginning of ovalbumin (OVA) sensitization or before OVA challenge decreased Th2 cytokines in the bronchoalveolar lavage fluid of OVA/alum-immunized allergic mice. In addition, the inhibitory effects of IL-21 on Th2 effector functions can also be found in allergic patients. Our results demonstrate that IL-21 suppresses the development of Th2 cells and functions of polarized Th2 cells. Hence, the administration of IL-21 may be considered for use as a preventive and therapeutic approach when dealing with Th2-mediated allergic diseases.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Lin
authors.forename: Hsiao-Yu
authors.initials: HY
authors.lastname: Jen
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
authors.forename: Fuu
authors.initials: F
authors.lastname: Sheu
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D019672:Genes, T-Cell Receptor; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D065631:Rhinitis, Allergic / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000098546:Interleukin-21
chemical_list: D018926:Anti-Allergic Agents; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D010047:Ovalbumin; D000098546:Interleukin-21
keywords: GATA3; IL-21; Th2; apoptosis; cytokines