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http://purl.uniprot.org/citations/15188362http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15188362http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Generalized DNA hypomethylation contributes to altered T cell function and gene expression in systemic lupus erythematosus (SLE). Some of the overexpressed genes participate in the disease process, but the full repertoire of genes affected is unknown. Methylation-sensitive T cell genes were identified by treating T cells with the DNA methyltransferase inhibitor 5-azacytidine and comparing gene expression with oligonucleotide arrays. CD70, a costimulatory ligand for B cell CD27, was one gene that reproducibly increased. We then determined whether CD70 is overexpressed on T cells treated with other DNA methylation inhibitors and on SLE T cells, and determined its functional significance.

Methods

Oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction, and flow cytometry were used to compare CD70 expression in T cells treated with 2 DNA methyltransferase inhibitors (5-azacytidine and procainamide) and 3 ERK pathway inhibitors known to decrease DNA methyltransferase expression (U0126, PD98059, and hydralazine). The consequences of CD70 overexpression were tested by coculture of autologous T and B cells with and without anti-CD70 and measuring IgG production by enzyme-linked immunosorbent assay. The results were compared with those of T cells from lupus patients.

Results

SLE T cells and T cells treated with DNA methylation inhibitors overexpressed CD70 and overstimulated B cell IgG production. The increase in IgG synthesis was abrogated by anti-CD70.

Conclusion

SLE T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. This increased B cell costimulation and subsequent immunoglobulin overproduction may contribute to drug-induced and idiopathic lupus."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.org/dc/terms/identifier"doi:10.1002/art.20255"xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Lu Q."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Deng C."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Richardson D."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Wu A."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Hanash S."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Richardson B."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/author"Oelke K."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/pages"1850-1860"xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/title"Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors."xsd:string
http://purl.uniprot.org/citations/15188362http://purl.uniprot.org/core/volume"50"xsd:string
http://purl.uniprot.org/citations/15188362http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15188362
http://purl.uniprot.org/citations/15188362http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15188362
http://purl.uniprot.org/uniprot/#_A0A0U5JA32-mappedCitation-15188362http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15188362
http://purl.uniprot.org/uniprot/#_P32970-mappedCitation-15188362http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15188362
http://purl.uniprot.org/uniprot/P32970http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15188362
http://purl.uniprot.org/uniprot/A0A0U5JA32http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15188362