FGFR2IIIb signaling regulates thymic epithelial differentiation.
Heterogeneous epithelial populations comprising the thymic environment influence early and late stages of T-cell development. The processes that regulate the differentiation of thymic epithelium and that are responsible for this heterogeneity are not well understood, although mesenchymal/epithelial interactions are clearly involved. Here, we show that targeted expression by thymocytes of an fibroblast growth factor receptor-2IIIb (FGFR2IIIb) ligand, FGF10, profoundly alters the differentiation and function of thymic epithelium (TE). Reconstitution of irradiated lckFGF10 mice with normal bone marrow restores normal thymic organization and function, while wild-type mice reconstituted with lckFGF10 bone marrow recapitulates some of the thymic alterations seen in lckFGF10 mice. We also demonstrate that interference with FGFR2IIIb signaling in the thymus with a soluble FGFR2IIIb dominant-negative fusion protein leads to precocious reductions in thymic size and cellularity that resemble age-related thymic involution. These findings indicate that TE compartments are dynamically maintained and that FGF signals are involved in this process.
Dooley
James
J
Department of Biological Structure, University of Washington, Seattle, Washington 98195-7420, USA.
Erickson
Matthew
M
Larochelle
William J
WJ
Gillard
Geoffrey O
GO
Farr
Andrew G
AG
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006801:Humans; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development* / Q000378:metabolism
D017931:DNA Primers; C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D020033:Protein Isoforms; D011994:Recombinant Proteins; D007633:Keratins; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2