Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1784910537887318016 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10031135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT rundbergnilssonalexandra temporaldynamicsoftnfmediatedchangesinhematopoieticstemcellfunctionandrecovery AT hidalgoisabel temporaldynamicsoftnfmediatedchangesinhematopoieticstemcellfunctionandrecovery AT bryderdavid temporaldynamicsoftnfmediatedchangesinhematopoieticstemcellfunctionandrecovery AT pronkcornelisjan temporaldynamicsoftnfmediatedchangesinhematopoieticstemcellfunctionandrecovery |