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 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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Nguyen HD,Ticer T,Bastian D,Kuril S,Li H,Du H,Yan C,Yu XZdoi
10.1016/j.celrep.2020.108316subject
Has Abstractpub_date
2020-10-27 00:00:00pages
108316issue
4issn
2211-1247pii
S2211-1247(20)31305-Xjournal_volume
33pub_type
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