Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration.
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.
Alpdogan
Onder
O
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hubbard
Vanessa M
VM
Smith
Odette M
OM
Patel
Neel
N
Lu
Sydney
S
Goldberg
Gabrielle L
GL
Gray
Daniel H
DH
Feinman
Jared
J
Kochman
Adam A
AA
Eng
Jeffrey M
JM
Suh
David
D
Muriglan
Stephanie J
SJ
Boyd
Richard L
RL
van den Brink
Marcel R M
MR
D000367:Age Factors; D000818:Animals; D016026:Bone Marrow Transplantation; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D038041:Lymphopoiesis / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D012038:Regeneration / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
D051523:Fibroblast Growth Factor 7