The Cyclic AMP Response Element Modulator α Suppresses CD86 Expression and APC Function

被引：23

作者：

Ahlmann, Martina ^{[1
,2
]}

Varga, Georg ^{[1
]}

Sturm, Karsten ^{[1
,3
]}

Lippe, Ralph ^{[1
,3
]}

Benedyk, Konrad ^{[1
,3
]}

Viemann, Dorothee ^{[1
]}

Scholzen, Thomas ^{[4
]}

Ehrchen, Jan ^{[1
]}

Mueller, Frank U. ^{[5
]}

Seidl, Matthias ^{[5
]}

Matus, Marek ^{[5
]}

Tsokos, George C. ^{[6
]}

Roth, Johannes ^{[1
,2
]}

Tenbrock, Klaus ^{[1
,3
,7
]}

机构：

[1] Univ Munster, Inst Immunol, Munster, Germany

[2] Univ Munster, Dept Pediat, Munster, Germany

[3] Univ Munster, Interdisziplinares Zentrum, Klin Forsch Res Grp, Munster, Germany

[4] Univ Munster, Inst Cell Biol, Munster, Germany

[5] Univ Munster, Inst Pharmacol & Toxicol, Munster, Germany

[6] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA

[7] Univ Aachen, Rhein Westfal TH Klinikum, Dept Pediat, Div Pediat Pulmonol Allergol & Immunol, D-52074 Aachen, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 07期

基金：

奥地利科学基金会;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELLS; IL-2; PRODUCTION; TRANSCRIPTIONAL REGULATION; DEPENDENT MECHANISM; ATOPIC-DERMATITIS; DENDRITIC CELLS; PROMOTER; BINDING; CREB;

D O I：

10.4049/jimmunol.0802976

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The cAMP response element modulator (CREM)a is a widely expressed transcriptional repressor that is important for the termination of the T cell immune response and contributes to the abnormal T cell function in patients with systemic lupus erythematosus. We present evidence that APCs of Crem(-/-) mice express increased amounts of the costimulatory molecule CD86 and induce enhanced Ag-dependent and Ag-independent T cell proliferation. Similarly, human APCs in which CREM alpha was selectively suppressed expressed more CD86 on the surface membrane. CREM alpha was found to bind to the CD86 promoter and suppressed its activity. Transfer of APCs from Crem(-/-) mice into naive mice facilitated a significantly stronger contact dermatitis response compared with mice into which APCs from Crem(-/-) mice had been transferred. We conclude that CREM alpha is an important negative regulator of costimulation and APC-dependent T cell function both in vitro and in vivo. The Journal of Immunology, 2009, 182: 4167-4174.

引用

页码：4167 / 4174

页数：8

共 34 条

[1]

The PI3 kinase, p38 SAP kinase, and NF-κB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells [J].

Ardeshna, KM ;

Pizzey, AR ;

Devereaux, S ;

Khwaja, A .

BLOOD, 2000, 96 (03) :1039-1046

[2]

Chromatin-dependent cooperativity between constitutive and inducible activation domains in CREB [J].

Asahara, H ;

Santoso, B ;

Guzman, E ;

Du, KY ;

Cole, PA ;

Davidson, I ;

Montminy, M .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (23) :7892-7900

[3]

Severe impairment of spermatogenesis in mice lacking the CREM gene [J].

Blendy, JA ;

Kaestner, KH ;

Weinbauer, GF ;

Nieschlag, E ;

Schutz, G .

NATURE, 1996, 380 (6570) :162-165

[4]

A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].

BOUSSIF, O ;

LEZOUALCH, F ;

ZANTA, MA ;

MERGNY, MD ;

SCHERMAN, D ;

DEMENEIX, B ;

BEHR, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301

[5]

Keratinocyte-derived, CD80-mediated costimulation is associated with hapten-specific IgE production during contact hypersensitivity to TH1 haptens [J].

Burns, R ;

Luzina, I ;

Nasir, A ;

Haidaris, CG ;

Barth, RK ;

Gaspari, AA .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (02) :383-390

[6]

Role of CBP/P300 in nuclear receptor signalling [J].

Chakravarti, D ;

LaMorte, VJ ;

Nelson, MC ;

Nakajima, T ;

Schulman, IG ;

Juguilon, H ;

Montminy, M ;

Evans, RM .

NATURE, 1996, 383 (6595) :99-103

[7]

Expanded population of activated antigen-engaged cells within the naive B cell compartment of patients with systemic lupus erythematosus [J].

Chang, Nan-Hua ;

VtclKenzie, Tamara ;

Bonventi, Galbriel ;

Landolt-Marticorena, Carolina ;

Fortin, Paul R. ;

Gladman, Dafna ;

Urowitz, Murray ;

Wither, Joan E. .

JOURNAL OF IMMUNOLOGY, 2008, 180 (02) :1276-1284

[8]

PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP [J].

CHRIVIA, JC ;

KWOK, RPS ;

LAMB, N ;

HAGIWARA, M ;

MONTMINY, MR ;

GOODMAN, RH .

NATURE, 1993, 365 (6449) :855-859

[9]

Transcriptional regulation by cyclic AMP-responsive factors [J].

De Cesare, D ;

Sassone-Corsi, P .

PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 64, 2000, 64 :343-369

[10]

Monocyte-derived dendritic cells over-express CD86 in patients with systemic lupus erythematosus [J].

Decker, Patrice ;

Koetter, Ina ;

Klein, Reinhild ;

Berner, Beate ;

Rammensee, Hans-Georg .

RHEUMATOLOGY, 2006, 45 (09) :1087-1095

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