Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice
Abstract
There is growing evidence that telomere dysfunction can contribute to human aging. Telomere dysfunction limits lymphopoiesis in aging telomerase knockout (mTerc−/−) mice primarily by the induction of stem cell–extrinsic alterations. The relative contribution of alterations in the stem cell niche and the systemic environment to the impairment of lymphopoiesis in response to telomere dysfunction is currently unknown. This study reveals a minor impact of stem cell–intrinsic defects on the impairment of B and T lymphopoiesis in response to telomere dysfunction. The impairment in B and T lymphopoiesis in aging telomere-dysfunctional mice was mainly due to alterations of the systemic environment. Telomere dysfunction had no significant cell-autonomous effects impairing the function of thymic or bone marrow niches in supporting B and T lymphopoiesis. Moreover, age-related alterations in the cellular composition of the thymic epithelium in telomere-dysfunctional mice were rescued by transplantation of the thymus into a wild-type environment; these rejuvenated thymi supported normal T lymphopoiesis in recipient mice. Together, these data place alterations in the systemic environment on top of the hierarchy of events limiting lymphopoiesis in response to telomere dysfunction.
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The causes of age-related decline in lymphocyte development are multifactorial, involving changes in hematopoietic stem cells and progenitors as well as local tissue and systemic environments.
“The causes of this age-related reduction in lymphocyte development are multifactorial and include changes in HSCs and progenitor cells (11,12) as well as the local tissue and systemic environments (13,14).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [14]
Systemic changes during aging may affect lymphocyte production and thymopoiesis.
“Systemic changes that occur during aging may also affect lymphocyte production (14) and thymopoiesis in particular.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [14]
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- Authors
- Song, Z., Wang, J., Guachalla, L. M., Terszowski, G., Rodewald, H.-R., Ju, Z., & Rudolph, K. L.
- Affiliations
- Universität Ulm (DE)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-02-25
- Volume
- 115
- Issue
- 8
- Pages
- 1481-1489
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2041375407
- Cited by
- 53
- References
- 12
- Citations by year
- 2023: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 6 · 2012: 9
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Connaught Fund
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- telomere dysfunction, lymphocyte development, B cell development, T lymphopoiesis, aging, thymic epithelium, thymus transplantation, bone marrow microenvironment, stem cell niche, thymic niche, cellular senescence
- MeSH terms
- Aging, Animals, B-Lymphocytes, Epithelium, Hematopoietic Stem Cells, Humans, RNA, T-Lymphocytes, Thymus Gland, Telomere, Mice, Knockout, Telomerase, Lymphopoiesis, Mice
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