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Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice.
MedLine Citation:
PMID:  22325374     Owner:  NLM     Status:  Publisher    
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.
Yasuyuki Negishi; Ayako Wakabayashi; Masumi Shimizu; Tomoko Ichikawa; Yoshihiro Kumagai; Toshiyuki Takeshita; Hidemi Takahashi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-13
Journal Detail:
Title:  Immunobiology     Volume:  -     ISSN:  1878-3279     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8002742     Medline TA:  Immunobiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier GmbH. All rights reserved.
Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan; Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo 113-8602, Japan.
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