Cutting edge: 4-1BB controls regulatory activity in dendritic cells through promoting optimal expression of retinal dehydrogenase.
J Immunol
; 189(6): 2697-701, 2012 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-22896640
ABSTRACT
Dendritic cells (DC) in the gut promote immune tolerance by expressing retinal dehydrogenase (RALDH), an enzyme that promotes retinoic acid, which aids differentiation of Foxp3+ inducible regulatory T cells (iTreg) in the intestinal mucosa. How RALDH expression is regulated is unclear. We found that 4-1BB (CD137), a member of the TNFR family, together with CD103, marked mesenteric lymph node DC with the highest level of RALDH activity, and ligation of 4-1BB maintained RALDH expression in these gut DC. Moreover, 4-1BB signals synergized with those through TLR2 or GM-CSFR to promote RALDH activity in undifferentiated DC. Correspondingly, 4-1BB-deficient mice were impaired in their ability to generate iTreg in the GALT when exposed to oral Ag, and 4-1BB-deficient mesenteric lymph node DC displayed weak RALDH activity and were poor at promoting iTreg development. Thus, our data demonstrate a novel activity of 4-1BB in controlling RALDH expression and the regulatory activity of DC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Regulação Enzimológica da Expressão Gênica
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Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
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Epitélio Pigmentado da Retina
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Gliceraldeído-3-Fosfato Desidrogenases
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos