Lysosomal Acid Lipase is a Potential Therapeutic Target for Controlling Gvhd after Allogeneic Hematopoietic Cell Transplantation in Mice

Graft-versus-host disease (GVHD) is a main barrier for the success of allogenic hematopoietic cell transplantation (allo-HCT). Lysosomal acid lipase (LAL) mediated cell-intrinsic lipolysis to generate free fatty acids and cholesterol in the cells. It plays an essential role in the development, proliferation and function of T cells. LAL deficiency decreases Th1 and Th2 differentiation while inducing the generation of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). Treg and MDSC are suppressive and Th1/Th2/memory CD8 cells are pathogenic in GVHD. LAL is also required for CD8 memory T cells development. Due to its importance in alloreactive T cell metabolism, we hypothesize that LAL is a valid potential target for the control of GVHD.