Regulation Of NK And JEG-3 Cells Function By Cyr61 And The Variation Of DC In HIV-1 Infected Patients

Cysteine rich 61 (Cyr61) is the first discovered member of the CCN protein family, mainly involved in regulating cell proliferation, migration, adhesion, cell survival, and ECM formation. The research found that Cyr61 was expressed rich in the placenta and was expressed at a significantly lower level in early-onset preeclamptic placentae and peripheral blood plasm compared with normal matched controls, suggesting that abnormal expression of Cyr61 may be involved in the pathogenesis of preeclampsia and provided the new diagnostic criteria. The study also found that NK cells in the uterus during pregnancy large gathering, may play an important role in the maintenance of immune balance in the maternal-fetal interface, and change of the NK cell number and function is closely related with preeclampsia. However, so far the regulation of Cyr61 on the NK cell and trophoblast cell is not clear. In addition, dendritic cells (DCs) are a kind of the most important professional antigen-presenting cells, and DCs play a pivotal role in the progress of human immunodeficiency virus 1 (HIV-1). Some studies found that the number of mDCs and pDCs was significantly lower in HIV-1 infection. However, the finding about the expression level of DC subsets in Chinese HIV-1 infected patients, in particular, DC subsets with different routes of transmission of HIV-1 infected patients have not been reported. In order to explore the effects of Cyr61 on the proliferation, activity and promoting tube-like formation of peripheral blood NK cells; analyze the regulation of Cyr61 on the proliferation of human choriocarcinoma cell line JEG-3 by regulating the expression of microRNA in the presence or absence of E2; investigate the relative expression of DC subsets (including monocytes, myeloid DC (mDC) precursors, myeloid DC (mDCs), plasma cells DCs (pDCs)) in different routes of transmission (including heterosexual, homosexual sexual contact, blood or blood products) of HIV-1 infection patients and correlation analysis with CD4+ T cells.Our results show:(1) Cyr61 promotes the proliferation of pNK cells, decreases the expression of CD16 receptor; increases the expression of KIR3DL1 inhibitory receptor and reduces the expression of NKG2D, NKp30 and CD244 activating receptor; promotes the KIR2DL1 inhibitory expression and suppresses the IFNγexpression and cytotoxicity of purified pNK; pNK cells can not promote the tube-like formation treated by Cyr61. (2) Endogenous Cyr61 protein is detected in JEG-3 cells; E2 can enhance the expression of Cyr61 mRNA; E2 and Cyr61 can promote the proliferation and reduce the expression of miR-195 of JEG-3 cells. (3) Compared with HIV-negative individuals (n=40), relative levels of Monocytes, CD11c+CD14-mDCs, CD11c+CD123low mDCs and CD11c-CD123+ pDCs among total peripheral blood mononuclear cells (PBMCs) are significantly lower in total HIV patients (n=93), and relative levels of CD11c+CD14-mDCs. CD11c+CD123low mDCs and CD11c-CD123+ pDCs among PBMCs are significantly lower in HIV patients through blood transmission (n=26), and relative levels of CD11c+CD14- mDCs, CD11c+CD123low mDCs, CD11c-CD123+ pDCs and monocytes among PBMCs are significantly lower in HIV patients through heterosexual transmission (n=43), and relative levels of monocytes, CD11c+CD14+ mDC precursors and CD11c+CD14- mDCs are significantly lower in HIV patients through homosexual transmission (n=24). The results of correlation analysis reveal significant negative correlations of the relative levels of blood mDC precursors both in total HIV and heterosexual transmission patients directly with CD4+ T cell counts. There are no significant correlation between mDCs and pDCs and CD4+ T cells counts with routes of transmission HIV patients. These results suggest that Cyr61 may be differentially regulated the signal transduction of lymphocytes pNK and purified pNK receptor; E2 may influence trophoblast cell function by enhancing the Cyr61 expression and decreasing the miR-195 expression in patients with preeclampsia; HIV-1 transmission may affect the distribution of DC subsets.In summary, We first study that the regulation of Cyr61 on the pNK cell and trophoblast cell; compare the relative expression of DC subsets with different routes of transmission of HIV-1 infected patients after highly active antiretroviral therapy (HAART). These findings provide important information for understanding the pathogenesis of preeclampsia and the role of DC in different HIV-1 infection groups.