Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA.
Nature
; 450(7167): 299-303, 2007 Nov 08.
Article
em En
| MEDLINE
| ID: mdl-18172933
ABSTRACT
Immune responses are normally targeted against microbial pathogens and not self-antigens by mechanisms that are only partly understood. Here we define a newly discovered pathway that prevents autoimmunity by limiting the levels on T lymphocytes of aco-stimulatory receptor, the inducible T-cell co-stimulator(ICOS). In sanroque mice homozygous for an M199R mutation in the ROQ domain of Roquin (also known as Rc3h1), increased Icos expression on T cells causes the accumulation of lymphocytes that is associated with a lupus-like autoimmune syndrome. Roquin normally limits Icos expression by promoting the degradation of Icos messenger RNA.A conserved segment in the unusually long ICOS 3' untranslated mRNA is essential for regulation by Roquin. This segment comprises a 47-base-pair minimal region complementary to T-cell-expressed microRNAs including miR-101, the repressive activity of which is disrupted by base-pair inversions predicted to abrogate miR-101 binding. These findings illuminate a critical post-transcriptional pathway within T cells that regulates lymphocyte accumulation and autoimmunity, and highlights the therapeutic potential of partially antagonising the ICOS pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Linfócitos T
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Antígenos de Diferenciação de Linfócitos T
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Autoimunidade
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Regulação da Expressão Gênica
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Ubiquitina-Proteína Ligases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália