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Objective To investigate the real-time regulatory effects of IFN-γ, programed death ligand 2(PDL2) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway on the adherence, proliferation and migration of human placenta-derived mesenchymal stem cells(hPMSCs) based on a finding that IFN-γ could enhance the expression of PDL2 in hPMSCs through JAK/STAT signaling pathway.Methods hPMSCs were isolated by using enzyme digestion method and then co-cultured with IFN-γ, anti-PDL2 monoclonal antibody (anti-PDL2 McAb) and JAK inhibitor, respectively.Real-time cell analysis (RTCA) was used to detect the dynamic changes in the adherence, proliferation and migration of hPMSCs following various interventions.Results IFN-γ remarkably suppressed hPMSCs proliferation during the period from 40 hours to 80 hours after intervention and also inhibited the non-targeted migration of hPMSCs.However, hPMSCs adherence was not affected by IFN-γ.Co-culturing hPMSCs with anti-PDL2 McAb significantly enhanced hPMSCs adhesion and inhibited their non-targeted migration, but had no significant effect on hPMSCs proliferation.Furthermore, the proliferation of hPMSCs co-cultured with IFN-γ and anti-PDL2 McAb was significantly inhibited as compared with that of anti-PDL2McAb treatment group.The adhesion, migration and proliferation of hPMSCs were significantly inhibited after co-culturing them with JAK inhibitor.Conclusion IFN-γ can remarkably suppress the proliferation and migration of hPMSCs.PDL2 can enhance the migration and inhibit the adhesion of hPMSCs.JAK/STAT signaling pathway is involved in regulating the adhesion, migration and proliferation of hPMSCs.
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Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells.
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Humanos , Basófilos , Células Dendríticas , Helmintos , Interleucina-4 , Linfocitos , Células TH1 , Células Th17 , Células Th2RESUMEN
Objective To investigate the regulatory effects of IFN-γon the expression of pro-grammed death ligand 2 (PDL2) on human placenta mesenchymal stem cells (hPMSCs) and the hPMSCs-induced differentiation of peripheral blood CD 8+IL-10+T cell subsets .Methods hPMSCs were isolated from mature human placenta by enzyme digestion .The expression of PDL2 on hPMSCs and the regulatory effects of IFN-γon PDL2 expression were detected by RT-PCR and flow cytometry ( FCM ) , respectively . Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects by density gradient centrif-ugation.T cells were purified with sheep red blood cells .FCM was used to detect the ratios of CD 8+IL-10+T cell subsets in PHA or CD3/CD28 beads activated T cells in the presence of hPMSCs treated with Anti-PDL2 McAb or IFN-γ.Results PDL2 molecules were highly expressed on hPMSCs that could be further enhanced by IFN-γ.The results of FCM demonstrated that hPMSCs could induce the differentiation of CD 8+IL-10+T cell subsets .The ratios of CD8+IL-10+T cell population in T cells activated by different stimulators including PHA and CD3/CD28 beads were significantly increased in the presence of hPMSCs as compared with those without hPMSCs (P<0.01).In addition, the antibody blocking experiments indicated that PDL 2 McAb down-regulated the percentages of CD 8+IL-10+T cell subsets in PHA or CD 3/CD28 beads stimulated T cells in the presence of hPMSCs as compared with those of unblocked groups .CD8+IL-10+T cell subsets were up-regulated in IFN-γtreated hPMSCs groups as compared with those of untreated groups .Conclusion hPMSCs could induce the differentiation of peripheral blood T cells into CD 8+IL-10+T cell subsets , which was enhanced by PDL 2 expressed on hPMSCs .IFN-γcould promote the differentiation of CD 8+IL-10+T cell subsets induced by hPMSCs through up-regulating the expression of PDL2 on hPMSCs.
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Objective To investigate the effect of programmed death ligand 2 (PDL2) in human placenta derived mesenchymal stem cells(hPMSCs) mediated immunoregulation on peripheral blood T cells activation,proliferation and cell cycle.Methods The expression of the PDL2 on hPMSCs was detected by RT-PCR,LSCM and FCM,respectively.Specific PDL2 siRNAs were transfected into hPMSCs via cathodolyte liposome transfection method.T cells were sorted from healthy peripheral blood by gradient centrifugation.The expression of early activation phenotype,proliferation and cell cycle of T cells were analyzed by FCM.Results PDL2 siRNA could effectively block the expression of PDL2 which was highly expressed on hPMSCs.The expression of CD69 on T cells had no significantly difference in blocking groups compared with unblocking groups.hPMSCs could inhibit the proliferation of T cells induced by PMA,compared with that of unblocking groups,the number of the T cells in G0/G1 phase was decreased while the number of the T cells in S phase was increased in the blocking groups.Conclusion PDL2 expressed on hPMSCs could promote the inhibitory effect of hPMSCs on T cell cycle and proliferation.