C., Cottrell J., Amaral L. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc AbbreviationsPEpreeclampsiaAT1\AAagonistic autoantibodies to the angiotensin II AT1 receptorTHT helperTregsT regulatory cellsNCRsnatural cytotoxicity receptorsdNK cellsdecidual NK cellsRUPPreduced uterine perfusion pressureNPnormal pregnant Introduction The hypertensive disorders of pregnancy complicate 6 to 11% of all pregnancies (Creasy autoantibody production, during pregnancy. Although this study demonstrated a role for memory B2 B lymphocytes in the pathogenesis of hypertension in response to placental ischaemia, it did not clarify antigenic stimulation or examine the role for the other B cell subtypes in the progression of this disease. B lymphocytes can be characterized as either B1 or B2 cells, GSK598809 each having distinct markers and roles in facilitating immune reactions. B1 lymphocytes can be further divided into B1a or B1b cells (Abbus and Lichtman, 2005; Liao CD40CCD40L binding is one important mechanism that leads to much of the pathophysiology of PE. Jensen studies of the activity of NK cells from patients with PE and normal pregnancies investigated the proliferative state and cytotoxic function of NK cells from maternal and cord blood. These studies demonstrated that the proliferative and killing ability of NK cells in PE patients was significantly higher than in normal third trimester pregnant women (Zhang em et al /em ., 2004). Mouse Monoclonal to His tag The increased number of cytotoxic NK cells in this study further supports the increased ratio of type 1 to type 2 NK cells in PE GSK598809 and may identify this cytotoxic population of type 1 NK cells as a therapeutic target in PE. Targeting the abnormal population of NK cells activated in PE may be a potential therapeutic option to improve treatment or management GSK598809 of PE. Although it is known that IL\2 and IL\12 signalling promote differentiation of NK cells to the NK1 subset, it has also been demonstrated that IL\17 may enhance cytolytic activity of NK cells, suggesting that TH17 cells may play a role in mediating differentiation into the NK1 population subset (Al Omar em et al /em ., 2013). IL\17 induced cytolytic NK cell activity against tumours which suggests a possible therapeutic strategy in cancer GSK598809 treatment (Qian em et al /em ., 2017). IL\17 was also shown to enhance NK cytolytic competence in fungal infection (Bar em et al /em ., 2014). Thus, blockade or neutralization of these cytokines may inhibit polarization of NK1 cells in PE. Additionally, expansion of the endogenous Treg population in PE may favour a type 2 shift in NK cells through decreasing IL\2\induced NK1 polarization. Conclusion The spectrum of hypertensive disorders of pregnancy is associated with inflammation and chronic immune activation. The immune profile of women with PE shifts from a controlled state of mild inflammation with a balance of both proinflammatory and anti\inflammatory components, to an altered state characterized by increased inflammatory cytokines and effector immune cells with a concomitant decrease in anti\inflammatory factors and regulatory cells (Figure ?(Figure2).2). Preclinical studies suggest that normalization of the immune imbalance in PE may be a potential strategy for the development of therapeutic interventions that could improve maternal and fetal outcomes associated with this maternal syndrome. Open in a separate window Figure 2 Placental ischaemia leads to an altered population of CD4+ T helper cells that facilitate B cell activation and NK cytolytic polarization leading to increased inflammatory cytokines and effector proteins. This in turn causes maternal system endothelial dysfunction resulting in the development of hypertension and intrauterine growth restriction (IUGR). Nomenclature of targets and ligands Key protein targets and ligands in this article are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Harding em et al /em ., 2018), and are permanently archived in the Concise Guide to PHARMACOLOGY 2017/18 (Alexander em et al /em ., 2017a, 2017b, 2017c). Conflict of interest The authors declare no conflicts of interest. Acknowledgement This study was supported by NIH grant RO1HD067541 (B.L.) and GSK598809 NIH grant HL130456 (D.C.). Notes Cornelius D. C., Cottrell J., Amaral L..
