Blocking miR-155 overexpression by donor T lymphocytes reduces GVHD in mice.
Scientists have identified microRNA-155 (miR-155) as a potential therapeutic target for preventing acute graft-versus-host disease (aGVHD) in leukemia patients receiving bone marrow transplants. Initial studies in mice by a team at Ohio State University found that the donor T cells of mice developing aGVHD following allogeneic hematopoietic stem cell transplant (alloHSCT) exhibit upregulated miR-155 expression. In a set of experiments designed to determine whether miR-155 plays a causal role in the development of aGVHD, the researchers then showed that animals receiving miR-155-deficient donor lymphocytes had markedly reduced lethal aGVHD. In contrast, lethal aGVHD developed rapidly in mice receiving miR-155 over-expressing T cells.
Moreover, blocking miR-155 expression by administering a synthetic anti-miR-155 following alloHSCT markedly decreased aGVHD severity and prolonged mouse survival. Reporting their results in Blood, Ramiro Garzon, M.D., and colleagues, say subsequent evaluation of large bowel biopsy samples from five patients with pathological evidence of intestinal aGVHD demonstrated upregulation of miR-155 by inflammatory T cells. Their published paper is titled “Regulation of acute graft-versus-host disease by microRNA-155.”
The researchers say their data indicate that overexpressoin of miR-155 is involved in controlling the severity of GVHD, and suggest the microRNA represents a promising therapeutic target. “Currently, acute GVHD is treated with high doses of steroids, which further increase the patient’s already high risk for infections, and then block the ability of the donor immune cells to fight the leukemia,” comments Professor Garzon, at Ohio State University’s Department of Internal Medicine and Comprehensive Cancer Center. “What is needed is a way to block acute GVHD without inhibiting the ability of transplanted cells to fight leukemia, and these findings suggest how that might be done.”