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12. Involvement of Innate Immunity in the Development of Inflammatory and Autoimmune Diseases

Author

TLASKALOVÁ-HOGENOVÁ, HELENA, primary, TUCKOVÁ, LUDMILA, additional, STEPÁNKOVÁ, RENATA, additional, HUDCOVIC, TOMÁS, additional, PALOVÁ-JELÍNKOVÁ, LENKA, additional, KOZÁKOVÁ, HANA, additional, ROSSMANN, PAVEL, additional, SANCHEZ, DANIEL, additional, CINOVÁ, JANA, additional, HRNČÍŘ, TOMÁS, additional, KVERKA, MILOSLAV, additional, FROLOVÁ, LENKA, additional, UHLIG, HOLM, additional, POWRIE, FIONA, additional, and BLAND, PAUL, additional

Published
2005
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13. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level

Author

Roncador, Giovanna, primary, Brown, Philip J., additional, Maestre, Lorena, additional, Hue, Sophie, additional, Martínez-Torrecuadrada, Jorge L., additional, Ling, Khoon-Lin, additional, Pratap, Sarah, additional, Toms, Christy, additional, Fox, Bridget C., additional, Cerundolo, Vincenzo, additional, Powrie, Fiona, additional, and Banham, Alison H., additional

Published
2005
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19. Control of intestinal inflammation by regulatory T cells

Author

Singh, Baljit, primary, Read, Simon, additional, Asseman, Chrystelle, additional, Malmström, Vivianne, additional, Mottet, Christian, additional, Stephens, Leigh A., additional, Stepankova, Renata, additional, Tlaskalova, Helena, additional, and Powrie, Fiona, additional

Published
2001
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26. Animal models of intestinal inflammation: clues to the pathogenesis of inflammatory bowel disease.

Author

Powrie F and Uhlig H

Subjects
Animals, CD4-Positive T-Lymphocytes immunology, Colitis immunology, Colitis pathology, Cytokines metabolism, Dendritic Cells cytology, Disease Models, Animal, Humans, Inflammation, Receptors, Interleukin-2 biosynthesis, Th1 Cells metabolism, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases physiopathology
Abstract

In the last decade a number of models of chronic intestinal inflammation have been described that resemble aspects of the pathology found in patients with inflammatory bowel disease. Several themes have emerged from these studies that are of relevance to the pathogenesis of inflammatory bowel disease. Firstly, intestinal inflammation is a consequence of an aberrant chronic immune response triggered by enteric bacteria. Both innate and adaptive immune mechanisms can cause colitis and in many models there is evidence of differential activation of T helper 1 (Th1)-type cells. Targeting the Th1 pathway prevents experimental colitis and there is also evidence that this may be useful in Crohn's disease. Secondly, specialized populations of regulatory T cells have been shown to prevent colitis and in some systems cure it, suggesting immune responses in the intestine are subject to dominant T cell-mediated control. Here we focus on new insights into the pathogenesis and regulation of intestinal inflammation as revealed by model systems and how these may be harnessed for the treatment of IBD.

Published
2004

27. Homing of intestinal immune cells.

Author

Uhlig HH, Mottet C, and Powrie F

Subjects
CD4-Positive T-Lymphocytes metabolism, Humans, Immune System, Inflammation, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases pathology, Integrins metabolism, Intestines cytology, Models, Biological, Peyer's Patches, Selectins metabolism, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Intestines immunology
Abstract

The homing of immune cells into the intestinal mucosa, the gut-associated lymphoid tissue or the mesenteric lymph nodes involves a complex process of molecular events that is dependent on cell type and cell maturation. Key factors that collectively determine the homing of leukocytes and their interaction with resident endothelial, epithelial, stromal and immune cells are interactions between integrins or selectins with their tissue adhesion molecules as well as chemokine receptors and their ligands. The organization of the small and large intestinal tissue and the mucosa associated lymphoid tissue as well as the presence or absence of inflammatory stimuli influence the homing of intestinal immune cells. The homing pattern of intestinal dendritic cells and CD4+ T cells and its role for the pathogenesis and regulation of inflammatory bowel disease are discussed.

Published
2004
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28. Control of immune pathology by regulatory T cells.

Author

Powrie F, Read S, Mottet C, Uhlig H, and Maloy K

Subjects
Adoptive Transfer, Animals, Antigens, CD, Antigens, Differentiation immunology, CD4 Antigens immunology, CTLA-4 Antigen, Colitis, Ulcerative immunology, Colitis, Ulcerative therapy, Humans, Inflammation immunology, Inflammation pathology, Inflammatory Bowel Diseases immunology, Mice, Mice, SCID, Receptors, Interleukin-2 immunology, Severe Combined Immunodeficiency therapy, Severe Combined Immunodeficiency immunology, Severe Combined Immunodeficiency pathology, T-Lymphocytes immunology, T-Lymphocytes pathology
Abstract

CD4+CD25+ T(reg) cells inhibit colitis in the severe combined immune deficient (SCID) T cell adoptive transfer model. Cells with this function are present in the thymus suggesting that T(reg) cells capable of inhibiting bacteria-induced immune pathology are similar to those that inhibit organ-specific autoimmunity. CD4+CD25+ T(reg) cells inhibit both T cell-dependent and T cell-independent intestinal inflammation. The latter point illustrates that in addition to direct effects on other T cells, T(reg) cells can alsoprevent immune pathology in vivo by inhibiting the actions of innate immune cells. T(reg) cells suppress intestinal inflammation through mechanisms that involve interleukin 10 and transforming growth factor beta and blockade of the negative regulator of T cell activation CTLA4 abrogates T(reg) cell function in vivo. Importantly adoptive transfer of CD4+CD25+ T(reg) cells to mice with established colitis reverses inflammation and restores normal intestinal architecture suggesting that CD4+CD25+ T(reg) cells may be utilized for cellular therapy of inflammatory diseases.

Published
2003

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