Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease.

ABSTRACT: Graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic cell transplantation (allo-HCT). Lysosomal acid lipase (LAL) mediates the intrinsic lipolysis of cells to generate free fatty acids (FFAs), which play an essential role in the development, proliferation, and function of T cells. Here, we find that LAL is essential for donor T cells to induce GVHD in murine models of allo-HCT. Specifically, LAL is required for donor T cell survival, differentiation, and alloreactivity in GVHD target organs, but not in lymphoid organs. LAL induces the differentiation of donor T cells toward GVHD pathogenic Th1/Tc1 and Th17 while suppressing regulatory T cell generation. LAL^-/- T cells succumb to oxidative stress and become anergic in target organs. Pharmacologically ta

SUBMITTER: Nguyen HD 

PROVIDER: S-EPMC7706352 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature