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Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease.
Nguyen, Hung D; Ticer, Taylor; Bastian, David; Kuril, Sandeepkumar; Li, Hong; Du, Hong; Yan, Cong; Yu, Xue-Zhong.
Afiliación
  • Nguyen HD; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Ticer T; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Bastian D; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Kuril S; Department of Pediatric Hematology-Oncology, Medical University of South Carolina, Charleston SC 29425, USA.
  • Li H; Department of Public Health, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Du H; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indianapolis, IN 46202, USA.
  • Yan C; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indianapolis, IN 46202, USA.
  • Yu XZ; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: yux@musc.edu.
Cell Rep ; 33(4): 108316, 2020 10 27.
Article en En | MEDLINE | ID: mdl-33113360
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esterol Esterasa / Linfocitos T Reguladores / Enfermedad Injerto contra Huésped Límite: Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esterol Esterasa / Linfocitos T Reguladores / Enfermedad Injerto contra Huésped Límite: Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos