David L. Owen, PhD, CRI Postdoctoral Fellow Harvard Medical School Area of Research: All Cancers, Colorectal Cancer Dr. Owen and his sponsor Dr. Mathis have found that a regulatory T cell subpopulation that is critical for tissue regeneration in injured muscle shows specificity for a self-protein found in the muscle and a dietary antigen found in the gut. His proposed studies aim to understand how this cross-specificity facilitates accumulation of gut-trained regulatory T cells into a distant site of injury. Improper control of inflammation drives the pathological loss of tissue function in numerous common conditions including cardiac arrest, fatty liver disease, and cancer. Following an injury, the immune system produces proinflammatory cytokines to initiate tissue regeneration. However, the magnitude and duration of inflammatory cytokines must be kept in check by a specialized subset of regulatory T cells that are trained in the gut. Without these regulatory T cells, the muscle fails to recover following injury, resulting in persistent inflammation and tissue fibrosis. Similar regulatory T cell subpopulation is found in liver inflammation and can even be found in the heart after cardiac arrest. While the drivers that allow accumulation of this population in a target tissue are unknown, the antigen specificity of regulatory T cells is critical to its differentiation and function. Understanding the cross-reactivity between intestinal and self-antigens will allow this critical subset of regulatory T cells to be exploited to enable more efficient control of tissue regeneration following damage or inflammation. Projects and Grants Control of Treg function by cross-reactivity between intestinal and self-antigens Harvard Medical School | All Cancers, Colorectal Cancer | 2023 | Diane J. Mathis, PhD
