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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hubbard
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Neel
authors.initials: N
authors.lastname: Patel
authors.forename: Sydney
authors.initials: S
authors.lastname: Lu
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Gray
authors.forename: Jared
authors.initials: J
authors.lastname: Feinman
authors.forename: Adam A
authors.initials: AA
authors.lastname: Kochman
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Eng
authors.forename: David
authors.initials: D
authors.lastname: Suh
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Muriglan
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boyd
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: 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*
chemical_list: D051523:Fibroblast Growth Factor 7