Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation

被引：172

作者：

Beyer, Marc ^{[1
]}

Thabet, Yasser ^{[1
]}

Mueller, Roman-Ulrich ^{[2
,3
]}

Sadlon, Timothy ^{[4
]}

Classen, Sabine ^{[1
]}

Lahl, Katharina ^{[5
,6
]}

Basu, Samik ^{[7
]}

Zhou, Xuyu ^{[8
,9
]}

Bailey-Bucktrout, Samantha L. ^{[8
,9
]}

Krebs, Wolfgang ^{[1
]}

Schoenfeld, Eva A. ^{[1
]}

Boettcher, Jan ^{[10
]}

Golovina, Tatiana ^{[7
]}

Mayer, Christian T. ^{[5
,6
]}

Hofmann, Andrea ^{[1
]}

Sommer, Daniel ^{[1
]}

Debey-Pascher, Svenja ^{[1
]}

Endl, Elmar ^{[10
]}

Limmer, Andreas ^{[10
]}

Hippen, Keli L. ^{[11
,12
]}

Blazar, Bruce R. ^{[11
,12
]}

Balderas, Robert ^{[13
]}

Quast, Thomas ^{[14
]}

Waha, Andreas ^{[15
]}

Mayer, Guenter ^{[16
]}

Famulok, Michael ^{[16
]}

Knolle, Percy A. ^{[10
]}

Wickenhauser, Claudia ^{[17
]}

Kolanus, Waldemar ^{[14
]}

Schermer, Bernhard ^{[2
,3
]}

Bluestone, Jeffrey A. ^{[8
,9
]}

Barry, Simon C. ^{[4
]}

Sparwasser, Tim ^{[5
,6
]}

Riley, James L. ^{[7
]}

Schultze, Joachim L. ^{[1
]}

机构：

[1] Univ Bonn, Lab Genom & Immunoregulat, Life & Med Sci Inst, D-5300 Bonn, Germany

[2] Univ Cologne, Div Renal, Dept Med, Cologne, Germany

[3] Univ Cologne, Ctr Mol Med, Cologne, Germany

[4] Univ Adelaide, Discipline Paediat, Womens & Childrens Hlth Res Inst, Adelaide, SA, Australia

[5] Hannover Med Sch, Inst Infect Immunol, TWINCORE, Ctr Expt & Clin Infect Res, D-3000 Hannover, Germany

[6] Helmholtz Ctr Infect Res, Hannover, Germany

[7] Univ Penn, Dept Microbiol, Translat Res Program, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[8] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[10] Univ Hosp Bonn, Inst Mol Med & Expt Immunol, Bonn, Germany

[11] Univ Minnesota, Cancer Ctr, Minneapolis, MN USA

[12] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA

[13] BD Biosci Pharmingen, San Diego, CA USA

[14] Univ Bonn, Life & Med Sci Inst, Lab Mol Immunol, D-5300 Bonn, Germany

[15] Univ Hosp Bonn, Dept Neuropathol, Bonn, Germany

[16] Univ Bonn, Life & Med Sci Inst, Biol Chem Lab, D-5300 Bonn, Germany

[17] Univ Hosp Leipzig, Dept Diagnost, Inst Pathol, Leipzig, Germany

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 09期

基金：

英国医学研究理事会;

关键词：

TRANSCRIPTION FACTOR FOXP3; TARGET GENES; BINDING PROTEIN; MULTIPLE GENES; TGF-BETA; IN-VIVO; EXPRESSION; PLASTICITY; IDENTIFICATION; DISRUPTION;

D O I：

10.1038/ni.2084

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Regulatory T cells (T-reg cells) are essential for self-tolerance and immune homeostasis. Lack of effector T cell (T-eff cell) function and gain of suppressive activity by T-reg cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T-reg cells. Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 39 untranslated region. Release of SATB1 from the control of Foxp3 in T-reg cells caused loss of suppressive function, establishment of transcriptional T-eff cell programs and induction of T-eff cell cytokines. Our data support the proposal that inhibition of SATB1-mediated modulation of global chromatin remodeling is pivotal for maintaining T-reg cell functionality.

引用

页码：898 / U125

页数：12

共 54 条

[21] Foxp3-Deficient Regulatory T Cells Do Not Revert into Conventional Effector CD4+ T Cells but Constitute a Unique Cell Subset [J].

Kuczma, Michal ;

Podolsky, Robert ;

Garge, Nikhil ;

Daniely, Danielle ;

Pacholczyk, Rafal ;

Ignatowicz, Leszek ;

Kraj, Piotr .

JOURNAL OF IMMUNOLOGY, 2009, 183 (06) :3731-3741

[22] Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease [J].

Lahl, Katharina ;

Loddenkemper, Christoph ;

Drouin, Cathy ;

Freyer, Jennifer ;

Arnason, Jon ;

Eberl, Gerard ;

Hamann, Alf ;

Wagner, Hermann ;

Huehn, Jochen ;

Sparwasser, Tim .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (01) :57-63

[23] Nonfunctional Regulatory T Cells and Defective Control of Th2 Cytokine Production in Natural Scurfy Mutant Mice [J].

Lahl, Katharina ;

Mayer, Christian T. ;

Bopp, Tobias ;

Huehn, Jochen ;

Loddenkemper, Christoph ;

Eberl, Gerard ;

Wirnsberger, Gerald ;

Dornmair, Klaus ;

Geffers, Robert ;

Schmitt, Edgar ;

Buer, Jan ;

Sparwasser, Tim .

JOURNAL OF IMMUNOLOGY, 2009, 183 (09) :5662-5672

[24] Developmental plasticity of Th17 and Treg cells [J].

Lee, Yun Kyung ;

Mukasa, Ryuta ;

Hatton, Robin D. ;

Weaver, Casey T. .

CURRENT OPINION IN IMMUNOLOGY, 2009, 21 (03) :274-280

[25] FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression [J].

Li, Bin ;

Samanta, Arabinda ;

Song, Xiaomin ;

Iacono, Kathryn T. ;

Bembas, Kathryn ;

Tao, Ran ;

Basu, Samik ;

Riley, James L. ;

Hancock, Wayne W. ;

Shen, Yuan ;

Saouaf, Sandra J. ;

Greene, Mark I. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (11) :4571-4576

[26] Regulatory T cell development in the absence of functional Foxp3 [J].

Lin, Wen ;

Haribhai, Dipica ;

Relland, Lance M. ;

Truong, Nga ;

Carlson, Marc R. ;

Williams, Calvin B. ;

Chatila, Talal A. .

NATURE IMMUNOLOGY, 2007, 8 (04) :359-368

[27] Dicer-dependent microRNA pathway safeguards regulatory T cell function [J].

Liston, Adrian ;

Lu, Li-Fan ;

O'Carroll, Donal ;

Tarakhovsky, Alexander ;

Rudensky, Alexander Y. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (09) :1993-2004

[28] Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein [J].

Lu, Li-Fan ;

Thai, To-Ha ;

Calado, Dinis Pedro ;

Chaudhry, Ashutosh ;

Kubo, Masato ;

Tanaka, Kentaro ;

Loeb, Gabriel B. ;

Lee, Hana ;

Yoshimura, Akihiko ;

Rajewsky, Klaus ;

Rudensky, Alexander Y. .

IMMUNITY, 2009, 30 (01) :80-91

[29] Identification of genes involved in the initiation of human Th1 or Th2 cell commitment [J].

Lund, R ;

Ahlfors, H ;

Kainonen, E ;

Lahesmaa, AM ;

Dixon, C ;

Lahesmaa, R .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (11) :3307-3319

[30] Foxp3 occupancy and regulation of key target genes during T-cell stimulation [J].

Marson, Alexander ;

Kretschmer, Karsten ;

Frampton, Garrett M. ;

Jacobsen, Elizabeth S. ;

Polansky, Julia K. ;

Maclsaac, Kenzie D. ;

Levine, Stuart S. ;

Fraenkel, Ernest ;

von Boehmer, Harald ;

Young, Richard A. .

NATURE, 2007, 445 (7130) :931-935

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