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ResearchIn-Press PreviewImmunologyStem cells
Open Access | 10.1172/JCI142842
1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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Vela, P.
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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Diaz-de-Heredia, C.
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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Sevilla, J.
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1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
Find articles by Rio, P. in: JCI | PubMed | Google Scholar
1Division of Innovative Therapies, CIEMAT and Advanced Therapies Unit, IIS-Fundación Jimenez Diaz and Autónoma University, Madrid, Spain
2Department of Pediatrics, University Hospital, University Duisburg-Essen, Essen, Germany
3Department of Genetics and Microbiology, Universitat Autónoma de Barcelona, Barcelona, Spain
4Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain
5Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Madrid, Spain
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Published June 7, 2022 - More info
Fanconi Anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, the pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since FA cells are defective in DNA repair, we hypothesized that FA hematopoietic stem and progenitor cells (HSPCs) might express DNA damage-associated stress molecules such as Natural Killer group 2 member D ligands (NKG2D-Ls). These ligands could then interact with the activating NKG2D receptor expressed in cytotoxic NK or CD8+ T cells which may result in progressive HSPCs depletion. Our results indeed demonstrated upregulated levels of NKG2D-Ls in cultured FA fibroblasts and T cells, which were further exacerbated by mitomycin C or formaldehyde. Notably, a high proportion of BM CD34+ HSPCs from FA patients also expressed increased levels of NKG2D-Ls, which correlated inversely with the percentage of CD34+ cells in BM. Remarkably, the reduced clonogenic potential characteristic of FA HSPCs was improved by blocking NKG2D/NKG2D-L interactions. Moreover, the in vivo blockage of these interactions in a BMF FA mouse model ameliorated the anemia in these animals. Our study demonstrates the involvement of NKG2D/NKG2D-L interactions in FA HSPC functionality, suggesting an unexpected role of the immune system in the progressive BMF characteristic of FA.