title: Notch signaling regulates the development of a novel type of Thy1-expressing dendritic cell in the thymus.
abstract: Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) required for T-cell activation and are classified into several subtypes by phenotypic and functional characteristics. However, it remains unclear if distinct transcription factors control the development of each DC subpopulation. In this report, we demonstrate that Notch signaling controls the development of a novel DC subtype that expresses Thy1 (Thy1(+) DCs). Overstimulation of bone marrow cells with the Notch ligand Delta-like 1 promoted the development of Thy1(+) DCs. Thy1(+) DCs are characterized as CD11c(+) MHC class II(+) NK1.1(-) B220(-) CD8α(+) , and are present in the thymus but not in the spleen and lymph nodes. Thymic Thy1(+) DCs are able to capture exogenous proteins and delete CD4(+) CD8(+) T cells. Transplantation experiments demonstrated that CD44(+) CD25(-) and CD44(+) CD25(+) thymocytes can differentiate into Thy1(+) DCs. Recombination signal binding protein for immunoglobulin kappa J region (RBP-J) deficiency in lineage-negative bone marrow cells, but not CD11c(+) cells, disrupted Thy1(+) DC development in the thymus. Our data indicate that Notch signaling controls the development of a novel type of Thy1-expressing DC in the thymus that possibly controls negative selection, and indicates that there may be highly regulated, differential transcriptional control of DC development. Furthermore, our findings suggest that Notch signaling regulates T-cell development not only by intrinsically inducing T-cell lineage-specific gene programs, but also by regulating negative selection through Thy1(+) DCs.
authors.affiliation: Department of Immunology and Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Ishifune
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Jun
authors.initials: J
authors.lastname: Nishida
authors.forename: Akiko
authors.initials: A
authors.lastname: Kitamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanigaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D039521:CD11c Antigen / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D018960:Hyaluronan Receptors; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D053645:Interleukin-2 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D018800:Thy-1 Antigens; C064045:delta protein