Friday, May 9, 2025
5/9/2025
Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease - Graft Versus Host Disease (GVHD) remains a significant issue in people receiving hematopoietic cell transplants to treat various cancers, genetic immunodeficiencies and other diseases. In GVHD, alloreactive T cells mediate this pathology, as T cell depleted hematopoietic transplants to not induce GVHD. We have observed that following transplantation, donor CD8 T cells undergo inflammasome activation, as measured by the activation of caspase‐1. However, these cells do not die via pyroptosis, which may alleviate their cytotoxic consequences in the host. We also observe that these cells in which the inflammasome is activated hyperexpress a protein, Ifi202, which is known to attenuate inflammasome activation, and human T cells similarly express IFI16, which functions similarly in human cells. We hypothesize that Ifi202 limits the degree of caspase‐1 activation in these cells, and thus prevents these cells from undergoing pyroptosis. The goal of this project is to determine the mechanism of inflammasome activation in these T cells, and to determine the role of Ifi202 in preventing pyroptosis in CD8 T cells during GVHD. We hypothesize that reduced Ifi202 expression in these cells will attenuate GVHD pathology by increasing pyroptosis in alloreactive CD8 T cells.
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