Trends in Molecular Medicine
ReviewCo-Signaling Molecules in Maternal–Fetal Immunity
Section snippets
Pregnancy, Immunology, and Co-Signaling Molecules
Pregnancy is a unique type of immunological process. To achieve successful pregnancy, the maternal immune system must accept the semiallogeneic (see Glossary) fetus that carries paternal antigens to allow for trophoblast invasion while preserving immune defense mechanisms against pathogens. However, the mechanisms controlling these unique immunological behaviors, and the harmonious crosstalk between maternal- and fetal-derived cells, remain poorly understood [1]. Given that dysregulation of
Co-Signaling Network
The concept of co-signals originated from the model of lymphocyte activation. According to the classic ‘two-signal model’ [7], lymphocytes remain unresponsive after exposure to the first signal, namely the recognition of antigens through T cell or B cell receptors (TCRs or BCRs). Lymphocytes are only fully activated after being stimulated by a second signal (co-signal) from the interaction between receptors on lymphocytes and their corresponding co-stimulating ligands on antigen-presenting cells
Co-Signaling Molecules in Human Pregnancy
Expression of Co-Signaling Molecules in Normal Pregnancy and RSA
At approximately 5 weeks after implantation, the human placenta is formed from both fetal-derived trophoblasts and the maternal-derived decidua. The placenta constitutes an interface connecting the mother and the fetus, which is known as the ‘maternal–fetal interface’ [23]. It is a highly dynamic tissue complementing the fetus, which develops rapidly through gestation, and it is the primary site of nutrient and gas exchange between
Co-Signaling Molecules in Murine Pregnancy
Murine models have also been used to gain further understanding of the role of co-signaling molecules in pregnancy. Indeed, in vivo blockade, deletion, or enhancement of co-signaling molecules, which could not be achieved in humans, could change the phenotype and function of maternal immune cells and lead to different pregnancy outcomes in such murine models. These, in turn, might link specific cellular processes to pathophysiological events and provide evidence that co-signaling-related immune
Concluding Remarks
The survival of a semiallogeneic fetus requires balanced maternal–fetal crosstalk, where immune regulation has an important role. Recent studies have shed new light on the involvement of co-signaling molecules in maternal–fetal immunity. These molecules are widely present at the maternal–fetal interface and are key immunomodulators providing the fetus with a suitable immunological microenvironment throughout pregnancy. They regulate the immunological and biological behaviors of embryonic
Acknowledgments
This study was supported by the National Basic Research Program of China (2015CB943300); National Nature Science Foundation of China (81630036, 91542116, 31570920, 81490744); the Key Project of Shanghai Municipal Education Commission (14ZZ013), and the Key Project of Shanghai Basic Research from Shanghai Municipal Science and Technology Commission (12JC1401600).
Glossary
- Allogeneic
- genetically dissimilar and, hence, immunologically incompatible between individuals of the same species.
- Antigen-presenting cells (APCs)
- display antigen complexes to T cells via TCRs. Professional APCs, including macrophages, B cells and dendritic cells, present foreign antigens to T helper cells, while other cell types can present antigens originating inside the cell to cytotoxic T cells.
- Basal plate
- during pregnancy, changes in the placenta involve the disappearance of the greater
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These authors contributed equally to this work.