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Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery

While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditio...

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Autores principales: Rundberg Nilsson, Alexandra, Hidalgo, Isabel, Bryder, David, Pronk, Cornelis Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031135/
https://www.ncbi.nlm.nih.gov/pubmed/36968066
http://dx.doi.org/10.1016/j.isci.2023.106341
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author Rundberg Nilsson, Alexandra
Hidalgo, Isabel
Bryder, David
Pronk, Cornelis Jan
author_facet Rundberg Nilsson, Alexandra
Hidalgo, Isabel
Bryder, David
Pronk, Cornelis Jan
author_sort Rundberg Nilsson, Alexandra
collection PubMed
description While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-renewal capacity of hematopoietic stem cells (HSCs), but its long-term effect on HSCs remains unclear. Here, we demonstrate that in vivo TNF administration results in a transient exit of HSCs from quiescence, which coincides with a compromised repopulation capacity. These functional changes are; however, fully reversible even following prolonged/chronic transient exposure to TNF. Notably, antagonizing TNF signaling in transplantation recipients enhances donor HSC reconstitution. Our findings provide molecular and functional insight into HSC regulation, with implications for both acute and chronic inflammatory conditions.
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spelling pubmed-100311352023-03-23 Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery Rundberg Nilsson, Alexandra Hidalgo, Isabel Bryder, David Pronk, Cornelis Jan iScience Article While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-renewal capacity of hematopoietic stem cells (HSCs), but its long-term effect on HSCs remains unclear. Here, we demonstrate that in vivo TNF administration results in a transient exit of HSCs from quiescence, which coincides with a compromised repopulation capacity. These functional changes are; however, fully reversible even following prolonged/chronic transient exposure to TNF. Notably, antagonizing TNF signaling in transplantation recipients enhances donor HSC reconstitution. Our findings provide molecular and functional insight into HSC regulation, with implications for both acute and chronic inflammatory conditions. Elsevier 2023-03-05 /pmc/articles/PMC10031135/ /pubmed/36968066 http://dx.doi.org/10.1016/j.isci.2023.106341 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rundberg Nilsson, Alexandra
Hidalgo, Isabel
Bryder, David
Pronk, Cornelis Jan
Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title_full Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title_fullStr Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title_full_unstemmed Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title_short Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery
title_sort temporal dynamics of tnf-mediated changes in hematopoietic stem cell function and recovery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031135/
https://www.ncbi.nlm.nih.gov/pubmed/36968066
http://dx.doi.org/10.1016/j.isci.2023.106341
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