PMID- 28779023
OWN - NLM
STAT- MEDLINE
DCOM- 20171010
LR  - 20201209
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 199
IP  - 6
DP  - 2017 Sep 15
TI  - Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by 
      Regulating Aldh1a2 Expression.
PG  - 1989-1997
LID - 10.4049/jimmunol.1700645 [doi]
AB  - Dendritic cells (DCs) are important for adaptive immune responses through the 
      activation of T cells. The molecular interplay between DCs and T cells determines 
      the magnitude of T cell responses or outcomes of functional differentiation of T 
      cells. In this study, we demonstrated that DCs in mice that are Rbpj deficient in 
      CD11c(+) cells (Rbpj(-/-) mice) promoted the differentiation of IL-17A-producing 
      Th17 cells. Rbpj-deficient DCs expressed little Aldh1a2 protein that is required 
      for generating retinoic acid. Those DCs exhibited a reduced ability for 
      differentiating regulatory T cells induced by TGF-beta. Rbpj protein directly 
      regulated Aldh1a2 transcription by binding to its promoter region. The 
      overexpression of Aldh1a2 in Rbpj-deficient DCs negated their Th17-promoting 
      ability. Transfer of naive CD4(+) T cells into Rag1-deficient Rbpj(-/-) mice 
      enhanced colitis with increased Th17 and reduced induced regulatory T cells 
      (iTreg) compared with control Rag1-deficient mice. The cotransfer of iTreg and 
      naive CD4(+) T cells into Rag1-deficient Rbpj(-/-) mice improved colitis compared 
      with transfer of naive CD4(+) T cell alone. Furthermore, cotransfer of DCs from 
      Rbpj(-/-) mice that overexpressed Aldh1a2 or Notch-stimulated DCs together with 
      naive CD4(+) T cells into Rbpj(-/-)Rag1-deficient mice led to reduced colitis 
      with increased iTreg numbers. Therefore, our studies identify Notch signaling in 
      DCs as a crucial balancer of Th17/iTreg, which depends on the direct regulation 
      of Aldh1a2 transcription in DCs.
CI  - Copyright (c) 2017 by The American Association of Immunologists, Inc.
FAU - Zaman, Taskia Sultana
AU  - Zaman TS
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Arimochi, Hideki
AU  - Arimochi H
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Maruyama, Satoshi
AU  - Maruyama S
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Ishifune, Chieko
AU  - Ishifune C
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Tsukumo, Shin-Ichi
AU  - Tsukumo SI
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Kitamura, Akiko
AU  - Kitamura A
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan.
FAU - Yasutomo, Koji
AU  - Yasutomo K
AD  - Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima 
      University, Tokushima 770-8503, Japan yasutomo@tokushima-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170804
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD11c Antigen)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Interleukin-17)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptors, Notch)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.2.1 (Aldehyde Dehydrogenase 1 Family)
RN  - EC 1.2.1.36 (ALDH1A2 protein, human)
RN  - EC 1.2.1.36 (Retinal Dehydrogenase)
SB  - IM
MH  - Aldehyde Dehydrogenase 1 Family
MH  - Animals
MH  - CD11c Antigen/metabolism
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Colitis/*immunology
MH  - Dendritic Cells/*immunology
MH  - Gene Expression Regulation
MH  - Genes, RAG-1
MH  - Humans
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics
MH  - Interleukin-17/metabolism
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Notch/metabolism
MH  - Retinal Dehydrogenase/genetics/*metabolism
MH  - T-Lymphocytes, Regulatory/*immunology/transplantation
MH  - Th17 Cells/*immunology
MH  - Tretinoin/metabolism
EDAT- 2017/08/06 06:00
MHDA- 2017/10/11 06:00
CRDT- 2017/08/06 06:00
PHST- 2017/05/04 00:00 [received]
PHST- 2017/07/06 00:00 [accepted]
PHST- 2017/08/06 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2017/08/06 06:00 [entrez]
AID - jimmunol.1700645 [pii]
AID - 10.4049/jimmunol.1700645 [doi]
PST - ppublish
SO  - J Immunol. 2017 Sep 15;199(6):1989-1997. doi: 10.4049/jimmunol.1700645. Epub 2017 
      Aug 4.