Arid
DOI10.1002/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
ISSN2326-5191
EISSN2326-5205
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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