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J Leukoc Biol ; 93(6): 963-72, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23547144

RESUMO

IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-ß production in the MLN and colon; had lower RORγt mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Anidrase Carbônica I/administração & dosagem , Colite/imunologia , Dessensibilização Imunológica/métodos , Subpopulações de Linfócitos T/imunologia , Administração Oral , Animais , Linfócitos T CD4-Positivos/transplante , Anidrase Carbônica I/imunologia , Colite/prevenção & controle , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Tolerância Imunológica/imunologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Reação em Cadeia da Polimerase em Tempo Real , Subpopulações de Linfócitos T/transplante
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