University of Kentucky
Role of Interleukin-17 in Intestinal Inflammation
Institution
University of Kentucky
Faculty Advisor/ Mentor
Scott Bryson
Abstract
Graft-versus-host-disease (GVHD) is a common complication of a genetically different or allogeneic bone marrow transplantation (BMT) in which graft cells elicit an immunological response that destroys host tissue. To inhibit the development of GVHD following allogeneic BMT, immunosuppressive agents such as cyclosporine A (CsA) were administered. Interestingly, CsA was also used to induce a GVHD-like disease in mice that had received a syngeneic or genetically identical bone marrow transplant. Syngeneic GVHD (SGVHD) was induced following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a 21-day course of CsA. The clinical symptoms of SGVHD were characterized by weight loss, runting, hunched posture, and severe diarrhea with target organs being the liver and colon. This model was utilized to study immune regulation and intestinal inflammation. Syngeneic GVHD is thought to be driven by the enhanced expression of specific pro-inflammatory cytokines. Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds, allowing one cell to communicate with another. The complex differentiation pathway of the naïve CD4+ T-helper cells involved a number of cytokine interactions. Until recently, it was thought that only two subsets of effector T-helper cells existed. However, recent studies have demonstrated the discovery of a third helper T-cell population, TH17, that produces the cytokine interleukin 17 (IL-17). IL-17 producing T-cells can drive various pathologies including intestinal inflammation. Preliminary studies in Dr. Scott Bryson’s laboratory have suggested involvement of TH17 T-cells in the pathology associated with SGVHD. Molecular, proteomic, and immunoblockade studies will be utilized to determine if TH17 immunity is involved in the development of SGVHD.
Role of Interleukin-17 in Intestinal Inflammation
Graft-versus-host-disease (GVHD) is a common complication of a genetically different or allogeneic bone marrow transplantation (BMT) in which graft cells elicit an immunological response that destroys host tissue. To inhibit the development of GVHD following allogeneic BMT, immunosuppressive agents such as cyclosporine A (CsA) were administered. Interestingly, CsA was also used to induce a GVHD-like disease in mice that had received a syngeneic or genetically identical bone marrow transplant. Syngeneic GVHD (SGVHD) was induced following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a 21-day course of CsA. The clinical symptoms of SGVHD were characterized by weight loss, runting, hunched posture, and severe diarrhea with target organs being the liver and colon. This model was utilized to study immune regulation and intestinal inflammation. Syngeneic GVHD is thought to be driven by the enhanced expression of specific pro-inflammatory cytokines. Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds, allowing one cell to communicate with another. The complex differentiation pathway of the naïve CD4+ T-helper cells involved a number of cytokine interactions. Until recently, it was thought that only two subsets of effector T-helper cells existed. However, recent studies have demonstrated the discovery of a third helper T-cell population, TH17, that produces the cytokine interleukin 17 (IL-17). IL-17 producing T-cells can drive various pathologies including intestinal inflammation. Preliminary studies in Dr. Scott Bryson’s laboratory have suggested involvement of TH17 T-cells in the pathology associated with SGVHD. Molecular, proteomic, and immunoblockade studies will be utilized to determine if TH17 immunity is involved in the development of SGVHD.