PMID- 21469122
OWN - NLM
STAT- MEDLINE
DCOM- 20110624
LR  - 20171116
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 41
IP  - 5
DP  - 2011 May
TI  - Notch signaling regulates the development of a novel type of Thy1-expressing 
      dendritic cell in the thymus.
PG  - 1309-20
LID - 10.1002/eji.201041159 [doi]
AB  - 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(-) CD8alpha(+) , 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.
CI  - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Ishifune, Chieko
AU  - Ishifune C
AD  - Department of Immunology and Parasitology, Institute of Health Biosciences, The 
      University of Tokushima Graduate School, Tokushima, Japan.
FAU - Maekawa, Yoichi
AU  - Maekawa Y
FAU - Nishida, Jun
AU  - Nishida J
FAU - Kitamura, Akiko
AU  - Kitamura A
FAU - Tanigaki, Kenji
AU  - Tanigaki K
FAU - Yagita, Hideo
AU  - Yagita H
FAU - Yasutomo, Koji
AU  - Yasutomo K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110412
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CD11c Antigen)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptors, Notch)
RN  - 0 (Thy-1 Antigens)
RN  - 0 (delta protein)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Blotting, Western
MH  - Bone Marrow Cells/metabolism
MH  - CD11c Antigen/analysis
MH  - Cell Differentiation
MH  - Dendritic Cells/classification/cytology/*immunology
MH  - Flow Cytometry
MH  - Hyaluronan Receptors
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein/deficiency
MH  - Interleukin-2 Receptor alpha Subunit/analysis
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lymphocyte Activation
MH  - Membrane Proteins/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Polymerase Chain Reaction
MH  - Receptors, Notch/genetics/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes
MH  - Thy-1 Antigens/*genetics/metabolism
MH  - Thymus Gland/cytology/embryology/*immunology
EDAT- 2011/04/07 06:00
MHDA- 2011/06/28 06:00
CRDT- 2011/04/07 06:00
PHST- 2010/10/12 00:00 [received]
PHST- 2011/01/21 00:00 [revised]
PHST- 2011/02/16 00:00 [accepted]
PHST- 2011/04/07 06:00 [entrez]
PHST- 2011/04/07 06:00 [pubmed]
PHST- 2011/06/28 06:00 [medline]
AID - 10.1002/eji.201041159 [doi]
PST - ppublish
SO  - Eur J Immunol. 2011 May;41(5):1309-20. doi: 10.1002/eji.201041159. Epub 2011 Apr 
      12.