Indispensable Role of the Runx1-Cbfβ Transcription Complex for In Vivo-Suppressive Function of FoxP3+ Regulatory T Cells

被引：197

作者：

Kitoh, Akihiko ^{[1
,2
]}

Ono, Masahiro ^{[1
,2
,3
]}

Naoe, Yoshinori

Ohkura, Naganari ^{[1
,3
,4
]}

Yamaguchi, Tomoyuki ^{[1
]}

Yaguchi, Hiroko ^{[1
,3
,4
]}

Kitabayashi, Issay ^{[5
]}

Tsukada, Toshihiko ^{[4
]}

Nomura, Takashi ^{[1
]}

Miyachi, Yoshiki ^{[2
]}

Taniuchi, Ichiro

Sakaguchi, Shimon ^{[1
,3
]}

机构：

[1] Kyoto Univ, Inst Frontier Med Sci, Dept Expt Pathol, Kyoto 6068507, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Dermatol, Kyoto 6068507, Japan

[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Expt Immunol Lab, Suita, Osaka 5650871, Japan

[4] Natl Canc Ctr, Res Inst, Tumor Endocrinol Project, Tokyo 1040045, Japan

[5] Natl Canc Ctr, Res Inst, Div Mol Oncol, Tokyo 1040045, Japan

来源：

IMMUNITY | 2009年 / 31卷 / 04期

关键词：

IMMUNOLOGICAL SELF-TOLERANCE; HELPER TYPE-1 CELLS; RUNX1; BINDING-SITE; MEDIATED SUPPRESSION; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; GENE-EXPRESSION; CUTTING EDGE; GRANZYME-B; REPRESSION;

D O I：

10.1016/j.immuni.2009.09.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Naturally arising regulatory T (Treg) cells express the transcription factor FoxP3, which critically controls the development and function of Treg cells. FoxP3 interacts with another transcription factor Runx1 (also known as AML1). Here, we showed that Treg cell-specific deficiency of Cbf beta, a cofactor for all Runx proteins, or that of Runx1, but not Runx3, induced lymphoproliferation, autoimmune disease, and hyperproduction of IgE. Cbfb-deleted Treg cells exhibited impaired suppressive function in vitro and in vivo, with altered gene expression profiles including attenuated expression of FoxP3 and high expression of interleukin-4. The Runx complex bound to more than 3000 gene loci in Treg cells, including the Foxp3 regulatory regions and the Il4 silencer. In addition, knockdown of RUNX1 showed that RUNX1 is required for the optimal regulation of FoxP3 expression in human T cells. Taken together, our results indicate that the Runx1-Cbf beta heterodimer is indispensable for in vivo Treg cell function, in particular, suppressive activity and optimal expression of FoxP3.

引用

页码：609 / 620

页数：12

共 45 条

[1] Role of RUNX in autoimmune diseases linking rheumatoid arthritis, psoriasis and lupus [J].