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

• Published in: The Journal of immunology (1950) Vol. 182; no. 7; pp. 4167 - 4174
• Main Authors: Ahlmann, Martina, Varga, Georg, Sturm, Karsten, Lippe, Ralph, Benedyk, Konrad, Viemann, Dorothee, Scholzen, Thomas, Ehrchen, Jan, Muller, Frank U, Seidl, Matthias, Matus, Marek, Tsokos, George C, Roth, Johannes, Tenbrock, Klaus
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-04-2009
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; B7-2 Antigen - genetics; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; Cyclic AMP Response Element Modulator - genetics; Cyclic AMP Response Element Modulator - immunology; Cyclic AMP Response Element Modulator - metabolism; Dermatitis, Contact - immunology; Dermatitis, Contact - pathology; Flow Cytometry; Gene Expression - immunology; Gene Expression Regulation - immunology; Humans; Lymphocyte Activation - immunology; Mice; Mice, Transgenic; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0802976

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.