دورية أكاديمية
أعرض في EDS

Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.

التفاصيل البيبلوغرافية
العنوان: Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.
المؤلفون: Li Q; Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China.; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Wang X; Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China.; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Song Q; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA.; Fujian Medical University Center of Translational Hematology, Fujian Institute of Hematology, and Fujian Medical University Union Hospital, Fuzhou, China., Yang S; Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China.; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Wu X; Department of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA., Yang D; Department of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA., Marié IJ; Department of Pathology, NYU Grossman School of Medicine, New York, USA., Qin H; Department of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA., Zheng M; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Nasri U; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Kong X; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Wang B; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA.; Fujian Medical University Center of Translational Hematology, Fujian Institute of Hematology, and Fujian Medical University Union Hospital, Fuzhou, China., Lizhar E; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA., Cassady K; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA., Tompkins J; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA., Levy D; Department of Pathology, NYU Grossman School of Medicine, New York, USA., Martin PJ; Fred Hutchinson Cancer Center, Seattle, Washington, USA., Zhang X; Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China., Zeng D; Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope, Duarte, California, USA.; Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, California, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2023 Aug 01; Vol. 133 (15). Date of Electronic Publication: 2023 Aug 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Graft vs Host Disease*/genetics , Graft vs Host Disease*/prevention & control , Leukemia*, Mice ; Animals ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes/metabolism ; Graft vs Leukemia Effect/genetics ; Bone Marrow Transplantation
مستخلص: STAT3 deficiency (STAT3-/-) in donor T cells prevents graft-versus-host disease (GVHD), but the impact on graft-versus-leukemia (GVL) activity and mechanisms of GVHD prevention remains unclear. Here, using murine models of GVHD, we show that STAT3-/- donor T cells induced only mild reversible acute GVHD while preserving GVL effects against nonsusceptible acute lymphoblastic leukemia (ALL) cells in a donor T cell dose-dependent manner. GVHD prevention depended on programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) signaling. In GVHD target tissues, STAT3 deficiency amplified PD-L1/PD-1 inhibition of glutathione (GSH)/Myc pathways that regulate metabolic reprogramming in activated T cells, with decreased glycolytic and mitochondrial ATP production and increased mitochondrial ROS production and dysfunction, leading to tissue-specific deletion of host-reactive T cells and prevention of GVHD. Mitochondrial STAT3 deficiency alone did not reduce GSH expression or prevent GVHD. In lymphoid tissues, the lack of host-tissue PD-L1 interaction with PD-1 reduced the inhibition of the GSH/Myc pathway despite reduced GSH production caused by STAT3 deficiency and allowed donor T cell functions that mediate GVL activity. Therefore, STAT3 deficiency in donor T cells augments PD-1 signaling-mediated inhibition of GSH/Myc pathways and augments dysfunction of T cells in GVHD target tissues while sparing T cells in lymphoid tissues, leading to prevention of GVHD while preserving GVL effects.
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معلومات مُعتمدة: P30 CA033572 United States CA NCI NIH HHS; R01 CA228465 United States CA NCI NIH HHS; R01 HL162847 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Adaptive immunity; Bone marrow transplantation; Hematology; T cells; Transplantation
المشرفين على المادة: 0 (CD274 protein, human)
0 (B7-H1 Antigen)
0 (Programmed Cell Death 1 Receptor)
SCR Disease Name: Thymic aplasia
تواريخ الأحداث: Date Created: 20230801 Date Completed: 20230802 Latest Revision: 20230804
رمز التحديث: 20230804
مُعرف محوري في PubMed: PMC10378157
DOI: 10.1172/JCI165723
PMID: 37526084
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI165723