Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease. Cell Rep 2020 Oct 27;33(4):108316
Date
10/29/2020Pubmed ID
33113360Pubmed Central ID
PMC7706352DOI
10.1016/j.celrep.2020.108316Scopus ID
2-s2.0-85094605461 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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 targeting LAL effectively prevents GVHD development while preserving the GVL activity. Thus, the present study reveals the role of LAL in T cell alloresponse and pathogenicity and validates LAL as a target for controlling GVHD and tumor relapse after allo-HCT.
Author List
Nguyen HD, Ticer T, Bastian D, Kuril S, Li H, Du H, Yan C, Yu XZAuthor
Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Graft vs Host DiseaseHumans
Sterol Esterase
T-Lymphocytes, Regulatory
