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ResearchIn-Press PreviewImmunologyTransplantation
Open Access | 10.1172/JCI125986
1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
Find articles by Ma, H. in: JCI | PubMed | Google Scholar
1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
Find articles by Wang, H. in: JCI | PubMed | Google Scholar
1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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Hoebe, K.
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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Pan, S.
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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1Columbia Center for Translational Immunology, Columbia University, New York, United States of America
2Division of Hematology/Oncology, Columbia University, New York, United States of America
3Department of Pathology and Cell Biology, Columbia University, New York, United States of America
4Department of Pathology and Cell Biology, George Washington University, Washington DC, United States of America
5Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, United States of America
6Cancer Biostatistics Shared Resource, Herbert Irving Columbia Cancer Center, New York, United States of America
7Columbia University, New York, United States of America
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Mapara, M.
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Published November 29, 2022 - More info
Absence of Interferon-γ Receptor (IFNGR) or Signal Transducer and Activator of Transcription 1 (STAT1) signaling in donor cells has been shown to result in reduced acute GVHD induction. In this study, we unexpectedly observed increased activation and expansion of donor lymphocytes in both lymphohematopoietic organs and GVHD target tissues of IFNGR/STAT1-deficient recipient mice, leading to rapid mortality following the induction of GVHD. Lipopolysaccharide (LPS)-matured bone marrow-derived Ifngr1-/-/Stat1-/- dendritic cells (BMDCs) were more potent allogeneic stimulators and expressed increased levels of MHC II and costimulatory molecules. Similar effects were observed in human APCs with knockdown of Stat1 by CRISPR/Cas9 and treatment with a JAK1/2 inhibitor. Furthermore, we demonstrated that the absence of IFNGR/STAT1 signaling in hematopoietic APCs impaired the presentation of exogenous antigens while promoting the presentation of endogenous antigens. In contrast, the indirect presentation of host antigens to donor lymphocytes was defective in IFNGR/STAT1-deficient donor-derived APCs in fully donor chimeric mice. The differential effects of IFNGR/STAT1 signaling on endogenous and exogenous antigen presentation could provide further insight into the roles of the IFN-γ/STAT1 signal pathway in the pathogenesis of GVHD, organ rejection, and autoimmune diseases.