Abstract | BACKGROUND & AIMS: METHODS: We examined the therapeutic action of DC(VIP) in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid, evaluating diverse clinical signs of the disease including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of DC(VIP), such as inflammatory cytokines and chemokines, Th1-type response, and the generation of regulatory T cells. RESULTS: DC(VIP) injection significantly ameliorated the clinical and histopathologic severity of colitis, abrogating body weight loss, diarrhea, and inflammation, and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response, by regulating a wide spectrum of inflammatory mediators directly through activated macrophages, and by generating interleukin-10-secreting regulatory T cells with suppressive capacity on autoreactive T cells. CONCLUSIONS: The possibility to generate/expand ex vivo regulatory DC(VIP) opens new therapeutic perspectives for the treatment of Crohn's disease in human beings, and may minimize the dependence on nonspecific immunosuppressive drugs used currently for autoimmune disorders.
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Authors | Elena Gonzalez-Rey, Mario Delgado |
Journal | Gastroenterology
(Gastroenterology)
Vol. 131
Issue 6
Pg. 1799-811
(Dec 2006)
ISSN: 0016-5085 [Print] United States |
PMID | 17087944
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Transforming Growth Factor beta
- Interleukin-10
- Vasoactive Intestinal Peptide
- Trinitrobenzenesulfonic Acid
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Topics |
- Animals
- Autoimmunity
- CD4-Positive T-Lymphocytes
(metabolism, pathology)
- Cell Transplantation
- Cells, Cultured
- Colitis
(chemically induced, metabolism, pathology, prevention & control)
- Dendritic Cells
(immunology, metabolism)
- Disease Models, Animal
- Immune Tolerance
- Immunotherapy
(methods)
- Interleukin-10
(metabolism)
- Mice
- Mice, Inbred BALB C
- Th1 Cells
(metabolism, pathology)
- Transforming Growth Factor beta
(metabolism)
- Trinitrobenzenesulfonic Acid
- Vasoactive Intestinal Peptide
(metabolism)
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