Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells

被引：63

作者：

Kanada, Shunsuke ^{[2
]}

Nishiyama, Chiharu ^{[1
]}

Nakano, Nobuhiro

Suzuki, Ryuyo

Maeda, Keiko

Hara, Mutsuko

Kitamura, Nao

Ogawa, Hideoki

Okumura, Ko ^{[2
]}

机构：

[1] Juntendo Univ, Sch Med, Atopy Allergy Res Ctr, Bunkyo Ku, Tokyo 1138421, Japan

[2] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan

来源：

BLOOD | 2011年 / 117卷 / 07期

关键词：

NF-KAPPA-B; T-CELLS; GENE-EXPRESSION; ALLOGRAFT SURVIVAL; COSTIMULATORY MOLECULE; REGULATORY FACTOR-4; COUNTER-RECEPTOR; CUTTING EDGE; MAST-CELLS; ACTIVATION;

D O I：

10.1182/blood-2010-06-291898

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cyto- kines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases. (Blood. 2011;117(7):2211-2222)

引用

页码：2211 / 2222

页数：12

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