RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla.
J Exp Med
; 204(6): 1267-72, 2007 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-17502664
ABSTRACT
Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4(+)3(-) inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4(+)3(-) cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire(+) mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance.
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Base de dados:
MEDLINE
Assunto principal:
Timo
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Fatores de Transcrição
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Linfócitos T CD4-Positivos
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Transdução de Sinais
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Autoimunidade
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Receptor Ativador de Fator Nuclear kappa-B
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article