Pre-B cell leukemia homeobox 1 is associated with lupus susceptibility in mice and humans.
J Immunol
; 188(2): 604-14, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22180614
ABSTRACT
Sle1a.1 is part of the Sle1 susceptibility locus, which has the strongest association with lupus nephritis in the NZM2410 mouse model. In this study, we show that Sle1a.1 results in the production of activated and autoreactive CD4(+) T cells. Additionally, Sle1a.1 expression reduces the peripheral regulatory T cell pool, as well as induces a defective response of CD4(+) T cells to the retinoic acid expansion of TGF-ß-induced regulatory T cells. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d overexpression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells and to decrease their apoptotic response to retinoic acid. PBX1-d is expressed more frequently in the CD4(+) T cells from lupus patients than from healthy controls, and its presence correlates with an increased central memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Proto-Oncogênicas
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Proteínas de Homeodomínio
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Predisposição Genética para Doença
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Proteínas de Ligação a DNA
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos