Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a T(h)17-independent manner.
Int Immunol
; 19(12): 1431-40, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17981790
ABSTRACT
Naive CD4(+) T cells rapidly proliferate to generate effector cells after encountering an antigen and small numbers survive as memory T cells in preparation for future immunological events. In the present work, adoptive transfer of naive CD4(+) T cells into RAG2(-/-) mice caused the generation of memory-type effector T cells including T(h)1, T(h)2, T(h)17 and regulatory T cells, and eventually induced T cell-dependent colitis. We found here that blocking of the IL-6R with a specific mAb remarkably inhibited the CD4(+) T cell-mediated colitis in parallel with the inhibition of T(h)17 cell generation. However, the transfer of naive CD4(+) T cells prepared from IL-17(-/-) mice still induced severe colitis. At the effector phase, the mAb significantly inhibited IL-17 but not IFN-gamma production. The blockade of IL-6 signaling enhanced the generation of IL-4- and IL-10-producing CD4(+) T cells, and inhibited up-regulation of tumor necrosis factor -alpha mRNA expression in the colon. These findings clearly demonstrated that IL-6 is a critical factor for the induction of colitis by expansion of naive CD4(+) T cells in RAG2(-/-) mice. Thus, the IL-6-mediated signaling pathway may be a significant therapeutic target in T cell-mediated autoimmune diseases.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Subpopulações de Linfócitos T
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Interleucina-6
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Interleucina-10
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Colite
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Receptores de Interleucina-6
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article