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DOI | 10.1002/art.38324 |
AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma t-Induced Th17 Cell Differentiation | |
Saito, Yukari1; Kagami, Shin-ichiro1,2; Sanayama, Yoshie1; Ikeda, Kei1; Suto, Akira1; Kashiwakuma, Daisuke2; Furuta, Shunsuke1,2; Iwamoto, Itsuo2; Nonaka, Ken3; Ohara, Osamu3; Nakajima, Hiroshi1 | |
通讯作者 | Kagami, Shin-ichiro |
来源期刊 | ARTHRITIS & RHEUMATOLOGY
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ISSN | 2326-5191 |
EISSN | 2326-5205 |
出版年 | 2014 |
卷号 | 66期号:5页码:1185-1194 |
英文摘要 | Objective. The proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6) and the Th17 cell cytokine IL-17A are implicated in the pathogenesis of rheumatoid arthritis (RA), and the blockade of these cytokines by biologic agents provides clinical benefits for RA patients. We undertook this study to clarify the mechanisms underlying the efficacy of IL-6 blockade in RA and to find a novel target for treatment of RA. Methods. We examined gene expression profiles of CD4+ T cells by DNA microarray analysis before and after treatment with an anti-IL-6 receptor antibody, tocilizumab (TCZ), in RA patients who exhibited good clinical responses to the treatment. Using murine CD4+ T cells, we then examined the roles of a newly identified molecule whose expression was significantly reduced in CD4+ T cells by TCZ therapy. We also examined the effect of the forced expression of the molecule on retinoic acid receptor-related orphan nuclear receptor gamma t (ROR gamma t)-induced IL-17A production in CD4+ T cells and on ROR gamma t-induced IL-17A promoter activation. Results. We identified AT-rich-interactive domain-containing protein 5A (ARID-5A) as a new molecule down-regulated by IL-6 blockade in the form of TCZ therapy. IL-6 induced the expression of ARID-5A in CD4+ T cells during Th17 cell differentiation by a STAT-3-dependent mechanism, whereas IL-6-induced ARID-5A expression was not affected by the absence of ROR gamma t, a lineage-specifying transcription factor of Th17 cells. Furthermore, ARID-5A physically associated with ROR gamma t through its N-terminal region and inhibited ROR gamma t-induced Th17 cell differentiation. Conclusion. ARID-5A is a lineage-specific attenuator of Th17 cell differentiation and may be involved in the pathogenesis of RA. |
类型 | Article |
语种 | 英语 |
国家 | Japan |
收录类别 | SCI-E |
WOS记录号 | WOS:000337363400015 |
WOS关键词 | RHEUMATOID-ARTHRITIS ; ARID PROTEINS ; DOUBLE-BLIND ; T(H)17 ; FAMILY ; TRANSCRIPTION ; SUPPRESSION ; CYTOKINES ; PATHOGENESIS ; GENERATION |
WOS类目 | Rheumatology |
WOS研究方向 | Rheumatology |
资源类型 | 期刊论文 |
条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/180867 |
作者单位 | 1.Chiba Univ, Chiba 2608670, Japan; 2.Asahi Gen Hosp, Chiba, Japan; 3.Kazusa DNA Res Inst, Chiba, Japan |
推荐引用方式 GB/T 7714 | Saito, Yukari,Kagami, Shin-ichiro,Sanayama, Yoshie,et al. AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma t-Induced Th17 Cell Differentiation[J],2014,66(5):1185-1194. |
APA | Saito, Yukari.,Kagami, Shin-ichiro.,Sanayama, Yoshie.,Ikeda, Kei.,Suto, Akira.,...&Nakajima, Hiroshi.(2014).AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma t-Induced Th17 Cell Differentiation.ARTHRITIS & RHEUMATOLOGY,66(5),1185-1194. |
MLA | Saito, Yukari,et al."AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma t-Induced Th17 Cell Differentiation".ARTHRITIS & RHEUMATOLOGY 66.5(2014):1185-1194. |
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