title: Thymic Epithelial Cells Are a Nonredundant Source of Wnt Ligands for Thymus Development.
abstract: Wnt signaling has been implicated in T cell development. However, it remained unclear which cell type is the major source of Wnt ligands and to what extent thymic epithelial cell (TEC) development is dependent on Wnt signaling. In this study, we analyzed the role of Wnt ligands provided by TECs for the development of T cells and TECs without manipulating the intracellular Wnt signaling machinery in either cell type. To this end, we used conditional knockout mice (FoxN1-Gpr177) in which TECs are unable to secrete Wnt ligands. Gpr177 (Evi/Wls) is a Wnt-specific cargo receptor that is required for the secretion of Wnt ligands. We found that TECs are the main source of Wnt ligands in the thymus, which serves a nonredundant role, and lack of TEC-provided Wnt ligands led to thymic hypotrophy, as well as a reduced peripheral T cell pool. Despite being reduced in numbers, T cells that developed in the absence of TEC-secreted Wnt ligands were functionally competent, and the subset composition of the peripheral T cell pool was not affected. Thus, our data suggest that T cell development is not directly dependent on TEC-provided Wnt ligands. Rather, TEC-secreted Wnt ligands are essential for normal thymus development and normal peripheral T cell frequencies but are dispensable for T cell function in the periphery.
authors.affiliation: Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Brunk
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, 69120 Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, 68167 Heidelberg, Germany; and.
authors.forename: Iris
authors.initials: I
authors.lastname: Augustin
authors.affiliation: Division of Molecular Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, 69120 Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, 68167 Heidelberg, Germany; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.affiliation: Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany; b.kyewski@dkfz-heidelberg.de.
authors.forename: Bruno
authors.initials: B
authors.lastname: Kyewski
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C090140:Whn protein; D051153:Wnt Proteins