Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging
Open accessAbstract
Age-related thymopoietic insufficiency has been proposed to be related to either defects in lymphohematopoietic progenitors or the thymic microenvironment. In this study, we examined whether keratinocyte growth factor (KGF), an epithelial cell–specific growth factor, could increase thymopoietic capacity in aged mice by restoration of the function of thymic epithelial cells (TECs). The thymic cellularity in KGF-treated aged mice increased about 4-fold compared to placebo-treated mice, resulting in an equivalent thymic cellularity to young mice. Enhanced thymopoiesis was maintained for about 2 months after a single course of KGF, and sustained improvement was achieved by administration of monthly courses of KGF. With the enhanced thymopoiesis after KGF treatment, the number of naive CD4 T cells in the periphery and T-cell–dependent antibody production improved in aged mice. KGF induced increased numbers of TECs and intrathymic interleukin-7 (IL-7) production and reorganization of cortical and medullary architecture. Furthermore, KGF enhanced thymopoiesis and normalized TEC organization in klotho (kl/kl) mice, a model of premature degeneration and aging, which displays thymopoietic defects. The result suggests that TEC damage is pathophysiologically important in thymic aging, and KGF therapy may be clinically useful in improving thymopoiesis and immune function in the elderly.
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FGF7 administration to old mice renews the thymic microenvironment, increases early T lineage progenitors, and restores thymus cellularity to young levels.
“FGF7 is particularly remarkable because its administration to old mice results in a renewal of the thymic microenvironment, increased numbers of ETPs, and a restoration of thymus cellularity to levels observed in the young (106, 107).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [106]
Fgf7 is particularly effective at restoring thymus cellularity in old mice to levels seen in young mice.
“Of the above factors, Fgf7 is particularly effective, because thymus cellularity in old mice administered multiple rounds of Fgf7 is restored to levels observed in the young.24”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [24]
The Fgf7 receptor is expressed on thymic stromal cells but not on thymocytes.
“A third category, typified by fibroblast growth factor 7 (Fgf7; also referred to as keratinocyte growth factor), binds to receptors expressed on thymic stromal cells but not thymocytes.[23][24][25]”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [24]
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References 75 · Cited by 214
Research works printed but not linked: 6
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- Authors
- Min, D., Panoskaltsis-Mortari, A., Kuro-o, M., Holländer, G. A., Blazar, B. R., & Weinberg, K. I.
- Affiliations
- Stanford Medicine (US)
- Division of Pediatric Bone Marrow Transplantation and Cancer Center, University of Minnesota, Minneapolis;
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas;
- Pediatric Immunology, Department of Research and Clinical-Biological Sciences, University of Basel, Switzerland
- University of Minnesota (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-11-30
- Volume
- 109
- Issue
- 6
- Pages
- 2529-2537
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1852207
- OpenAlex
- W2069539680
- Cited by
- 214
- References
- 75
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 6 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 9 · 2013: 16 · 2012: 11
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Ellison Medical Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (68310, 3100-68310.02)
- Eisai
- National Institutes of Health
- U.S. Public Health Service (A1057477)
- National Institute on Aging (AG25326, R01AG025326, AG-19712, R01AG019712)
- National Heart, Lung, and Blood Institute (HL 54729, P01HL073104, HL 70005, HL73104, R01HL070005, HL073 794, R01HL073794, R01HL054729)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- keratinocyte growth factor, thymopoiesis, thymic aging, thymic epithelial cells, thymic microenvironment, IL-7, naive CD4+ T cells, T cell-dependent antibody production, thymic cellularity
- MeSH terms
- Klotho Proteins, Aging, Animals, Cell Differentiation, Epithelial Cells, Female, Glucuronidase, Mice, Inbred C57BL, Thymus Gland, Interleukin-7, Models, Animal, Mice, Fibroblast Growth Factor 7
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