PMID- 19843945
OWN - NLM
STAT- MEDLINE
DCOM- 20091209
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 9
DP  - 2009 Nov 1
TI  - Constitutive expression of IDO by dendritic cells of mesenteric lymph nodes: 
      functional involvement of the CTLA-4/B7 and CCL22/CCR4 interactions.
PG  - 5608-14
LID - 10.4049/jimmunol.0804116 [doi]
AB  - Dendritic cells (DCs) express the immunoregulatory enzyme IDO in response to 
      certain inflammatory stimuli, but it is unclear whether DCs express this enzyme 
      under steady-state conditions in vivo. In this study, we report that the DCs in 
      mesenteric lymph nodes (MLNs) constitutively express functional IDO, which 
      metabolizes tryptophan to kynurenine. In line with a previous report that 
      regulatory T cells (Tregs) can induce IDO in DCs via the CTLA-4/B7 interaction, a 
      substantial proportion of the MLN DCs were located in juxtaposition to Tregs, 
      whereas this tendency was not observed for splenic DCs, which do not express IDO 
      constitutively. When CTLA-4 was selectively deleted in Tregs, the frequency of 
      IDO-expressing DCs in MLNs decreased significantly, confirming CTLA-4's role in 
      IDO expression by MLN DCs. We also found that the MLN DCs produced CCL22, which 
      can attract Tregs via CCR4, and that the phagocytosis of autologous apoptotic 
      cells induced CCL22 expression in CCL22 mRNA-negative DCs. Mice genetically 
      deficient in the receptor for CCL22, CCR4, showed markedly reduced IDO expression 
      in MLN-DCs, supporting the involvement of the CCL22/CCR4 axis in IDO induction. 
      Together with our previous observation that MLN DCs contain much intracytoplasmic 
      cellular debris in vivo, these results indicate that reciprocal interactions 
      between the DCs and Tregs via both B7/CTLA-4 and CCL22/CCR4 lead to IDO induction 
      in MLN DCs, which may be initiated and/or augmented by the phagocytosis of 
      autologous apoptotic cells by intestinal DCs. Such a mechanism may help induce 
      the specific milieu in MLNs that is required for the induction of oral tolerance.
FAU - Onodera, Toshiharu
AU  - Onodera T
AD  - Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka 
      University Graduate School of Medicine, Suita, Japan.
FAU - Jang, Myoung Ho
AU  - Jang MH
FAU - Guo, Zijin
AU  - Guo Z
FAU - Yamasaki, Mikako
AU  - Yamasaki M
FAU - Hirata, Takako
AU  - Hirata T
FAU - Bai, Zhongbin
AU  - Bai Z
FAU - Tsuji, Noriko M
AU  - Tsuji NM
FAU - Nagakubo, Daisuke
AU  - Nagakubo D
FAU - Yoshie, Osamu
AU  - Yoshie O
FAU - Sakaguchi, Shimon
AU  - Sakaguchi S
FAU - Takikawa, Osamu
AU  - Takikawa O
FAU - Miyasaka, Masayuki
AU  - Miyasaka M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Ccl22 protein, mouse)
RN  - 0 (Ccr4 protein, mouse)
RN  - 0 (Chemokine CCL22)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Receptors, CCR4)
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/metabolism/*physiology
MH  - B7-1 Antigen/metabolism/*physiology
MH  - CTLA-4 Antigen
MH  - Chemokine CCL22/metabolism/*physiology
MH  - Dendritic Cells/*enzymology/*immunology/metabolism/pathology
MH  - Female
MH  - Immune Tolerance/genetics
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis/*genetics/metabolism
MH  - Leukopenia/genetics/immunology
MH  - Lymph Nodes/enzymology/*immunology/metabolism/pathology
MH  - Mesentery
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Receptors, CCR4/metabolism/*physiology
EDAT- 2009/10/22 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/10/22 06:00
PHST- 2009/10/22 06:00 [entrez]
PHST- 2009/10/22 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 183/9/5608 [pii]
AID - 10.4049/jimmunol.0804116 [doi]
PST - ppublish
SO  - J Immunol. 2009 Nov 1;183(9):5608-14. doi: 10.4049/jimmunol.0804116.