PMID- 22325374
OWN - NLM
STAT- MEDLINE
DCOM- 20130108
LR  - 20131121
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 217
IP  - 10
DP  - 2012 Oct
TI  - Disruption of maternal immune balance maintained by innate DC subsets results in 
      spontaneous pregnancy loss in mice.
PG  - 951-61
LID - 10.1016/j.imbio.2012.01.011 [doi]
AB  - Dendritic cells (DCs) play an important role in providing an appropriate 
      fetal/maternal balance between Th1 and Th2 during pregnancy. The Th1/Th2 balance 
      seems to be regulated mainly by two distinct DC subsets, DEC-205(+) DCs having 
      the capacity to establish Th1 polarization and 33D1(+) DCs to induce Th2 
      dominance. Pregnancy is established and maintained by maternal hormones, such as 
      progesterone and estrogen, and the balance of DC subtypes was affected mainly by 
      progesterone, which induced a dose-dependent reduction of the DEC-205/33D1 ratio 
      together with/without a stable amount of estrogen. The DEC-205/33D1 ratio 
      decreased gradually with the progress of pregnancy and rapid augmentation of the 
      ratio was seen around delivery in vivo. Here, we demonstrate that depletion of 
      33D1(+) DCs during the perinatal period caused substantial fetal loss probably 
      mediated through Th1 up-regulation via transient IL-12 secretion, and 
      pre-administration of progesterone could rescue the fetal loss. Similar 
      miscarriages were also observed when pregnant mice were intraperitoneally (i.p.) 
      injected twice with IL-12 on Gd 9.5 and 10.5. Moreover, prior inoculation of 
      progesterone suppressed the enhanced serum IL-12 production in mice treated with 
      33D1 antibody, indicating that progesterone might inhibit temporal IL-12 
      secretion around Gd 10.5 and miscarriage was avoided. These findings suggest the 
      importance of balancing DC subsets during pregnancy and reveal that we can avoid 
      miscarriage by manipulating the activity of the DC subpopulation of pregnant 
      individuals with maternal hormones.
CI  - Copyright (c) 2012 Elsevier GmbH. All rights reserved.
FAU - Negishi, Yasuyuki
AU  - Negishi Y
AD  - Department of Microbiology and Immunology, Nippon Medical School, Bunkyo-ku, 
      Tokyo 113-8602, Japan.
FAU - Wakabayashi, Ayako
AU  - Wakabayashi A
FAU - Shimizu, Masumi
AU  - Shimizu M
FAU - Ichikawa, Tomoko
AU  - Ichikawa T
FAU - Kumagai, Yoshihiro
AU  - Kumagai Y
FAU - Takeshita, Toshiyuki
AU  - Takeshita T
FAU - Takahashi, Hidemi
AU  - Takahashi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120113
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cytokines)
RN  - 187348-17-0 (Interleukin-12)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Abortion, Spontaneous/chemically induced/*immunology
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage/immunology
MH  - Bone Marrow Cells/drug effects/immunology
MH  - Cytokines/blood/immunology
MH  - Dendritic Cells/drug effects/*immunology/metabolism
MH  - Estradiol/pharmacology
MH  - Female
MH  - Interleukin-12/administration & dosage
MH  - Kinetics
MH  - Lymphocyte Activation/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Progesterone/pharmacology
MH  - Spleen/cytology/immunology
MH  - T-Lymphocyte Subsets/immunology
MH  - Uterus/cytology/immunology
EDAT- 2012/02/14 06:00
MHDA- 2013/01/09 06:00
CRDT- 2012/02/14 06:00
PHST- 2011/06/06 00:00 [received]
PHST- 2011/11/19 00:00 [revised]
PHST- 2012/01/06 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2013/01/09 06:00 [medline]
AID - S0171-2985(12)00015-0 [pii]
AID - 10.1016/j.imbio.2012.01.011 [doi]
PST - ppublish
SO  - Immunobiology. 2012 Oct;217(10):951-61. doi: 10.1016/j.imbio.2012.01.011. Epub 
      2012 Jan 13.