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Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice
Authors:Yasuyuki Negishi  Tomoko Ichikawa  Toshiyuki Takeshita  Hidemi Takahashi
Affiliation:1. Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan;2. Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan
Abstract:Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC‐205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α‐galactosylceramide (α‐GalCer). Here we demonstrate that the adoptive transfer of DEC‐205+ bone marrow‐derived DCs cocultured with α‐GalCer (DEC‐205+ BMDCs‐c/w‐α‐GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium. Further, the adoptive transfer of NK1.1+ iNKT cells obtained from B6 mice injected with α‐GalCer facilitated miscarriages in syngeneic Jα18(?/?) (iNKT cell‐deficient) mice. These results suggest that DEC‐205+ DCs and NK1.1+ iNKT cells play crucial roles required for the initiation of fetal loss associated with stimulation by glycolipid antigens and sterile inflammation.
Keywords:Adoptive transfer  Dendritic cell (DC)  Invariant NKT cell (iNKT cell)  Miscarriage  α  ‐galactosylceramide (α  ‐GalCer)
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