Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion
Open accessAbstract
Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1Rs), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes, and thymic epithelial cells (TECs) in normal and genetically altered mice. In thymus-intact but not thymectomized mice, IGF-1 administration increased peripheral naive and recent thymic emigrant (RTE) populations, demonstrating its effect on T-cell production, not peripheral expansion. IGF-1 administration increased bone marrow LSK (lineage−, Sca-1+, c-kit+) precursor proliferation and peripheral LSK populations, increased thymocyte populations in a sequential wave of expansion, and proportionately expanded TEC subpopulations and enhanced their chemokine expression. To separate IGF-1's effects on thymocytes and TECs, we generated mice lacking IGF-1R on thymocytes and T cells. Thymocyte and RTE numbers were decreased in these mice, but IGF-1 treatment produced comparable thymocyte numbers to similarly treated wild-type mice. We additionally separated thymic- from LSK-specific effects by demonstrating that IGF-1 increased thymocyte numbers despite impaired early thymic progenitor (ETP) importation in PSGL-1KO mice. These results indicate the critical point thymic function regulation by IGF-1 involves TEC expansion regulating thymocyte precursor entry and facilitating thymocyte development.
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IGF-1 administration to old mice enhances thymopoiesis mainly through effects on thymic epithelial cells rather than thymocytes.
“Administration of IGF-1 to old mice enhances thymopoiesis predominantly through effects on thymic epithelial cells and not thymocytes (104).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [104]
The effects of growth hormone in human subjects likely resulted from induction of IGF-1 that acted similarly to IGF-1 in mice.
“The latter observations suggest that GH in the human subjects resulted in an induction of IGF-1 that functioned in a similar manner.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [104]
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Causes, consequences, and reversal of immune system aging
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- Authors
- Chu, Y.-W., Schmitz, S., Choudhury, B., Telford, W., Kapoor, V., Garfield, S., Howe, D., & Gress, R. E.
- Affiliations
- Center for Cancer Research (US)
- National Institutes of Health (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-10-01
- Volume
- 112
- Issue
- 7
- Pages
- 2836-2846
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2556619
- OpenAlex
- W1989969635
- Cited by
- 107
- References
- 53
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 2 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 10
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin-like growth factor I, thymopoiesis, thymic epithelial cells, IGF-1 receptor, T cell development, recent thymic emigrants, naive T cells, LSK cells, PSGL-1, chemokine expression, thymus
- MeSH terms
- Animals, Bone Marrow Cells, Cell Count, Cell Cycle, Cell Differentiation, Epithelial Cells, Hematopoietic Stem Cells, Humans, Insulin-Like Growth Factor I, Membrane Glycoproteins, Mice, Inbred C57BL, T-Lymphocytes, Thymus Gland, Signal Transduction, Receptor, IGF Type 1, Mice, Knockout, Chemokines, Cell Lineage, Cell Proliferation, Mice
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