Therapeutic targeting of the intestinal barrier in inflammatory bowel disease and graft-versus-host disease

Published on December 31, 2015   19 min
0:00
Hello, my name is Sam Nalle, I'm a postdoctoral fellow at Genentech, and I'll be discussing therapeutic targeting of the intestinal barrier in inflammatory bowel disease and graft-versus-host disease.
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In this lecture I will compare and contrast inflammatory bowel disease, IBD, and graft-versus-host disease, GVHD. I'll take a detailed look at the intestinal barrier in IBD and GVHD and I will discuss therapeutic targeting of the intestinal barrier in IBD and GVHD. The goal of this lecture is to understand the biological basis for rational therapeutic targeting of the intestinal barrier in IBD and GVHD.
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Starting with inflammatory bowel disease, IBD is comprised of Crohn's disease and ulcerative colitis. Ulcerative colitis involves only the colon whereas Crohn's disease can affect the entire gastrointestinal tract. Symptoms include malabsorption, nausea, bloody or mucoid diarrhea, and weight loss. Etiology involves a combination of genetic and environmental factors, and IBD is more prevalent in developed countries in North America and Europe.
1:08
I'll give the histology of Crohn's disease for some more detailed description of IBD. Inactive IBD is characterized by crypt architectural distortion, fibrosis, or epithelial metaplasia, but no active inflammatory infiltrates such as neutrophils or eosinophils. Mild activity is characterized by rare intraepithelial neutrophils or eosinophils, and increased numbers of neutrophils or eosinophils within the lamina propria. Moderate activity contains frequent intraepithelial neutrophils or eosinophils, lamina propria distortion, and markedly increased numbers of neutrophils or eosinophils within the lamina propria. Finally, severe activity is characterized by numerous crypt abscesses, erosions or ulcerations and focal sheets of neutrophils or eosinophils within the lamina propria.
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Turning to graft-versus-host disease, GVHD is the major complication associated with hematopoietic stem cell transplantation, or HSCT. HSCT is the term used with humans and BMT is the more general term that is often used in animal model studies. The transplantation procedure involves a harvest of donor stem cells, either directly from the bone marrow or by mobilization of stem cells by injection with G-CSF and harvesting peripheral blood, followed by infusion into a conditioned recipient. Prior to transplant, the recipient is treated with chemotherapy and/or radiation, which acts to immunosuppress the recipient to prevent graft rejection, reduce the number of tumor cells if applicable, reduce the number of recipient hematopoietic cells or to make space. A pre-transplant regimen is absolutely essential to the transplantation process but it contributes to GVHD, and that's a point I will discuss in more detail a little bit later in the lecture.
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Therapeutic targeting of the intestinal barrier in inflammatory bowel disease and graft-versus-host disease

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