Antigen presentation safeguards the integrity of the hematopoietic stem cell pool
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
5 May 2022
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| In: |
Cell stem cell
Year: 2022, Jahrgang: 29, Heft: 5, Pages: 760-775.e10 |
| ISSN: | 1875-9777 |
| DOI: | 10.1016/j.stem.2022.04.007 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.stem.2022.04.007 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1934590922001606 
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| Verfasserangaben: | Pablo Hernández-Malmierca, Dominik Vonficht, Alexandra Schnell, Hannah J. Uckelmann, Alina Bollhagen, Mohamed A. A. Mahmoud, Sophie-Luise Landua, Elise van der Salm, Christine L. Trautmann, Simon Raffel, Florian Grünschläger, Raphael Lutz, Michael Ghosh, Simon Renders, Nádia Correia, Elisa Donato, Karin O. Dixon, Christoph Hirche, Carolin Andresen, Claudia Robens, Paula S. Werner, Tobias Boch, David Eisel, Wolfram Osen, Franziska Pilz, Adriana Przybylla, Corinna Klein, Frank Buchholz, Michael D. Milsom, Marieke A. G. Essers, Stefan B. Eichmüller, Wolf-Karsten Hofmann, Daniel Nowak, Daniel Hübschmann, Michael Hundemer, Christian Thiede, Lars Bullinger, Carsten Müller-Tidow, Scott A. Armstrong, Andreas Trumpp, Vijay K. Kuchroo, Simon Haas |
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| 245 | 1 | 0 | |a Antigen presentation safeguards the integrity of the hematopoietic stem cell pool |c Pablo Hernández-Malmierca, Dominik Vonficht, Alexandra Schnell, Hannah J. Uckelmann, Alina Bollhagen, Mohamed A. A. Mahmoud, Sophie-Luise Landua, Elise van der Salm, Christine L. Trautmann, Simon Raffel, Florian Grünschläger, Raphael Lutz, Michael Ghosh, Simon Renders, Nádia Correia, Elisa Donato, Karin O. Dixon, Christoph Hirche, Carolin Andresen, Claudia Robens, Paula S. Werner, Tobias Boch, David Eisel, Wolfram Osen, Franziska Pilz, Adriana Przybylla, Corinna Klein, Frank Buchholz, Michael D. Milsom, Marieke A. G. Essers, Stefan B. Eichmüller, Wolf-Karsten Hofmann, Daniel Nowak, Daniel Hübschmann, Michael Hundemer, Christian Thiede, Lars Bullinger, Carsten Müller-Tidow, Scott A. Armstrong, Andreas Trumpp, Vijay K. Kuchroo, Simon Haas |
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| 520 | |a Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4+ T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4+ T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool. | ||
| 650 | 4 | |a acute myeloid leukemia | |
| 650 | 4 | |a antigen presentation | |
| 650 | 4 | |a CD4 T cells | |
| 650 | 4 | |a hematopoietic stem cells | |
| 650 | 4 | |a immune regulation | |
| 650 | 4 | |a immunosurveillance | |
| 650 | 4 | |a leukemia | |
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