Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 13, Issue 5, Pages 615-627Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2015.41
Keywords
CCL2; MDSCs; tolerance in pregnancy; trophoblast cells
Categories
Funding
- National Natural Science Foundation of China [31470885, 31270971, 81300510, 31300752, 31100650]
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Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal-maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14(+) myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14(+)HLA-DR-/low cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14(+) myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14(+)HLA-DR-/low MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14(+) myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy.
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