Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration Journal Article

Authors: Alpdogan, O.; Hubbard, V. M.; Smith, O. M.; Patel, N.; Lu, S.; Goldberg, G. L.; Gray, D. H.; Feinman, J.; Kochman, A. A.; Eng, J. M.; Suh, D.; Muriglan, S. J.; Boyd, R. L.; van den Brink, M. R. M.
Article Title: Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration
Abstract: Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the thymus. We studied the role of KGF in T-cell development with KGF -/- mice and demonstrated that thymic cellularity and the distribution of thymocyte subsets among KGF -/-, wildtype (WT), and KGF +/- mice were similar. However, KGF -/- mice are more vulnerable to sublethal irradiation (450 cGy), and a significant decrease was found in thymic cellularity after irradiation. Defective thymopoiesis and peripheral T-cell reconstitution were found in KGF -/- recipients of syngeneic or allogeneic bone marrow transplant, but using KGF -/- mice as a donor did not affect T-cell development after transplantation. Despite causing an early developmental block in the thymus, administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF also accelerated thymic recovery after irradiation, cyclophosphamide, and dexamethasone treatment. Finally, we found that administering KGF before bone marrow transplantation (BMT) resulted in enhanced thymopoiesis and peripheral T-cell numbers in middle-aged recipients of an allogeneic BM transplant. We conclude that KGF plays a critical role in postnatal thymic regeneration and may be useful in treating immune deficiency conditions. © 2006 by The American Society of Hematology.
Keywords: controlled study; nonhuman; protein function; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; animal tissue; cell maturation; cyclophosphamide; dexamethasone; allogenic bone marrow transplantation; age factors; wild type; regeneration; thymus; thymus gland; irradiation; immune deficiency; perinatal development; bone marrow transplantation; lymphopoiesis; thymocyte; fibroblast growth factor 7; lymphocyte count; perinatal period; palifermin
Journal Title: Blood
Volume: 107
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2006-03-15
Start Page: 2453
End Page: 2460
Language: English
DOI: 10.1182/blood-2005-07-2831
PUBMED: 16304055
PROVIDER: scopus
PMCID: PMC1895735
Notes: --- - "Cited By (since 1996): 72" - "Export Date: 4 June 2012" - "CODEN: BLOOA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Sydney X Lu
    98 Lu
  2. Odette Marsinay Smith
    98 Smith
  3. David Suh
    43 Suh
  4. Adam Kochman
    45 Kochman
  5. Vanessa Marie Hubbard
    42 Hubbard
  6. Neel Patel
    7 Patel
  7. Jeffrey Eng
    36 Eng