PMID- 20211938
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20181113
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 115
IP  - 2
DP  - 2010 Jun
TI  - Effects of TCDD on the fate of naive dendritic cells.
PG  - 422-34
LID - 10.1093/toxsci/kfq063 [doi]
AB  - The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes 
      immune suppression via activation of the aryl hydrocarbon receptor. Dendritic 
      cells (DCs), the professional antigen-presenting cells in the immune system, are 
      adversely affected by TCDD. We hypothesized that TCDD alters DC homeostasis, 
      resulting in a loss of DCs in naive mice. To test this hypothesis, C57Bl/6 mice 
      were gavaged with either vehicle or an immunosuppressive dose of TCDD (15 
      microg/kg). TCDD exposure decreased the frequency and number of splenic 
      CD11c(high) DCs on day 7 when compared with vehicle-treated controls. TCDD 
      increased the expression of CD86 and CD54, while decreasing the frequency of 
      splenic CD11c(high) DCs expressing CD11a and major histocompatibility complex 
      (MHC) class II. Moreover, TCDD selectively decreased the 
      CD11c(high)CD8alpha(-)33D1(+) splenic DCs specialized at activating CD4(+) T 
      cells but did not affect the regulatory CD11c(high)CD8alpha(+)DEC205(+) splenic 
      DCs. TCDD did not alter the number or frequency of CD11c(low) splenic DCs but 
      decreased their MHC class II and CD11a expression. Loss of splenic CD11c(high) 
      DCs was independent of Fas-mediated apoptosis and was not due to alterations in 
      the numbers of common DC precursors in the bone marrow or their ability to 
      generate steady-state DCs in vitro. Instead, increased CCR7 expression on 
      CD11c(high) DCs suggested involvement of a migratory event. Popliteal and 
      brachial lymph node CD11c(+) cells showed elevated levels of MHC class II and 
      CD40 following TCDD exposure. Collectively, this study shows the presence of a 
      TCDD-sensitive splenic DC subpopulation in naive mice, suggesting that TCDD may 
      induce suppression of T-cell-mediated immunity by disrupting DC homeostasis.
FAU - Bankoti, Jaishree
AU  - Bankoti J
AD  - Department of Biomedical and Pharmaceutical Sciences, University of Montana, 
      Missoula, Montana 59812, USA.
FAU - Burnett, Andrea
AU  - Burnett A
FAU - Navarro, Severine
AU  - Navarro S
FAU - Miller, Andrea K
AU  - Miller AK
FAU - Rase, Ben
AU  - Rase B
FAU - Shepherd, David M
AU  - Shepherd DM
LA  - eng
GR  - R01 ES013784/ES/NIEHS NIH HHS/United States
GR  - R01 ES013784-04/ES/NIEHS NIH HHS/United States
GR  - P20 RR17670/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100308
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Antigens, CD)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, CCR7)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Apoptosis/drug effects
MH  - Bone Marrow Cells/drug effects/pathology
MH  - Cell Count
MH  - Dendritic Cells/*drug effects/metabolism/pathology
MH  - Environmental Pollutants/*toxicity
MH  - Female
MH  - Lymph Nodes/*drug effects/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Receptors, CCR7/metabolism
MH  - Spleen/*drug effects/pathology
PMC - PMC2871756
EDAT- 2010/03/10 06:00
MHDA- 2010/08/11 06:00
PMCR- 2011/06/01
CRDT- 2010/03/10 06:00
PHST- 2010/03/10 06:00 [entrez]
PHST- 2010/03/10 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - kfq063 [pii]
AID - 10.1093/toxsci/kfq063 [doi]
PST - ppublish
SO  - Toxicol Sci. 2010 Jun;115(2):422-34. doi: 10.1093/toxsci/kfq063. Epub 2010 Mar 8.