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An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation Barrette Kathleen – Dreesen Erwin Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F
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Background
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Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis
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Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis
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Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis
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Murine models CD45RB high CD4+ T-cells C o l i t i s
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CD45RB low CD4+ T cells T reg CD45RB high CD4+ T cells T h 1 Immune- suppressive Immune- stimulative
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Question?
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The role of IL-10 in IBD? “Is there evidence that IL-10 plays an important role in mucosal immune regulation?” IL-10 knock-out mice enterocolitis (Kühn et al. 1993) rIL-10 administration no colitis in SCID mice restored with CD45RB high CD4+ T cells (Powrie et al. 1994) CD45RB high CD4+ T cells, isolated from transgenic mice that expressed IL-10 under the IL-2 promotor failed to transfer colitis, but rather were able to inhibit colitis induced by WT CD45RB high CD4+ T cells (Hagenbaugh et al. 1997)
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Experimental evidence?
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IL-10 -/- mice T reg ? Treatment with anti-IL-10(R) mAb colitis? Colitis T 1 h cells secreting IFN-g and TNF-a in the lesions
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IL-10 -/- mice T reg ? Treatment with anti-IL-10(R) mAb colitis? Colitis T 1 h cells secreting IFN-g and TNF-a in the lesions
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CD45RB high CD4+ T-cells C o l i t i s
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RAG-2 -/- mice 10-12 wk WT CD45RB high CD4+ T-cells C o l i t i s
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RAG-2 -/- mice 10-12 wk WT C o l i t i s W CD45RB high CD4+ T-cells CD45RB low CD4+ T-cells
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C o l i t i s
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RAG-2 -/- mice 10-12 wk C o l i t i s W CD45RB low CD4+ T-cells IL-10 -/- WT CD45RB high CD4+ T-cells
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C o l i t i s
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RAG-2 -/- mice 10-12 wk C o l i t i s W CD45RB low CD4+ T-cells IL-10 -/-
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