The Cyclic AMP Response Element Modulator {alpha} Suppresses CD86 Expression and APC Function

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Mar 21

PMID 19299714

Citations 8

Authors

Martina Ahlmann

Georg Varga

Karsten Sturm

Ralph Lippe

Konrad Benedyk

Dorothee Viemann

Thomas Scholzen

Jan Ehrchen

Frank U Muller

Matthias Seidl

Marek Matus

George C Tsokos

Johannes Roth

Klaus Tenbrock

Affiliations

Soon will be listed here.

Abstract

The cAMP response element modulator (CREM)alpha 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 CREMalpha was selectively suppressed expressed more CD86 on the surface membrane. CREMalpha 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 CREMalpha is an important negative regulator of costimulation and APC-dependent T cell function both in vitro and in vivo.

Citing Articles

Novel Aspects of cAMP-Response Element Modulator (CREM) Role in Spermatogenesis and Male Fertility.

Sanchez-Jasso D, Lopez-Guzman S, Bermudez-Cruz R, Oviedo N Int J Mol Sci. 2023; 24(16).

PMID: 37628737 PMC: 10454534. DOI: 10.3390/ijms241612558.

CREM Alpha Enhances IL-21 Production in T Cells and .

Ohl K, Wiener A, Lippe R, Schippers A, Zorn C, Roth J Front Immunol. 2017; 7:618.

PMID: 28066428 PMC: 5165720. DOI: 10.3389/fimmu.2016.00618.

The cAMP response element modulator (CREM) regulates TH2 mediated inflammation.

Verjans E, Ohl K, Reiss L, van Wijk F, Toncheva A, Wiener A Oncotarget. 2015; 6(36):38538-51.

PMID: 26459392 PMC: 4770719. DOI: 10.18632/oncotarget.6041.

cAMP responsive element modulator: a critical regulator of cytokine production.

Rauen T, Hedrich C, Tenbrock K, Tsokos G Trends Mol Med. 2013; 19(4):262-9.

PMID: 23491535 PMC: 3891595. DOI: 10.1016/j.molmed.2013.02.001.

cAMP-responsive element modulator α (CREMα) contributes to decreased Notch-1 expression in T cells from patients with active systemic lupus erythematosus (SLE).

Rauen T, Grammatikos A, Hedrich C, Floege J, Tenbrock K, Ohl K J Biol Chem. 2012; 287(51):42525-32.

PMID: 23124208 PMC: 3522254. DOI: 10.1074/jbc.M112.425371.

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