The immune system of pregnant women is tightly controlled to defend against microbial infections and at the same time, to accept an embryo or the fetus, which are expressing semi-allogenic paternal antigens. Furthermore, inflammation-like processes are crucial for tissue growth, remodeling, and differentiation of the decidua during pregnancy. Dysregulation of elaborate immune control may lead reproductive failure, such as implantation failure, recurrent pregnancy loss (RPL), preterm birth, intrauterine fetal growth restriction, and preeclampsia. Until recent years, a balance between Th1 and Th2 cells was believed to be the key immune regulatory mechanism of T-cell immunology especially during pregnancy. Since the identification of regulatory T cells was made, the mechanism of immune regulation has become a major issue in immunologic research. Also, the recent identification of Th17 cells has drawn our attention to a new immune effector. The balance between Th17 and regulatory T cells may explain more about the pathophysiology of reproductive failure. This review will discuss relevant human literature on regulatory T and Th17 cells in normal reproductive physiology and in women with RPL and infertility.
served the cause of surgical science well. Our understanding of basic disease mechanisms and insights into potential new therapeutic strategies have occurred at a staggering pace. Perhaps nowhere in surgical biology are these mechanistic insights and therapeutic prospects more evident than in research defining the cytokine mediators of inflammation, injury, and repair. These proteins are secreted to some degree by virtually all immune cell types as well as by a diverse array of other nucleated cells, and their functions encompass a regulatory role on and among many components of the immune system. Such intense interest is well deserved because abnormalities or dysregulation of tissue and wound repair as well as of natural (innate) or specific (acquired) immune function underlie much of the morbidity and mortality associated with surgical practice. Indeed, it is evident that the insights gained from the study of such inflammatory mediators cross virtually every specialty of surgery, from the acute sequelae of severe injury and invasive infection to the chronic manifestations of benign and malignant processes.1,2
The complement system is an important mediator of the acute inflammatory response, and an effective inhibitor would suppress tissue damage in many autoimmune and inflammatory diseases. Such an inhibitor might be found among the endogenous regulatory proteins of complement that block the enzymes that activate C3 and C5. Of these proteins, complement receptor type 1 (CR1; CD35) has the most inhibitory potential, but its restriction to a few cell types limits its function in vivo. This limitation was overcome by the recombinant, soluble human CR1, sCR1, which lacks the transmembrane and cytoplasmic domains. The sCR1 bivalently bound dimeric forms of its ligands, C3b and methylamine-treated C4 (C4-ma), and promoted their inactivation by factor I. In nanomolar concentrations, sCR1 blocked complement activation in human serum by the two pathways. The sCR1 had complement inhibitory and anti-inflammatory activities in a rat model of reperfusion injury of ischemic myocardium, reducing myocardial infarction size by 44 percent. These findings identify sCR1 as a potential agent for the suppression of complement-dependent tissue injury in autoimmune and inflammatory diseases.
