Abstract:Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Further, it has been reported that PD-1 ligands (PD-Ls) contribute to M2 polarization of macrophages and their immunosuppressive effects. Total glucosides of paeony… Show more
“…Therefore, repairing the dynamic balance between Th1/Th2/Th17/Treg cells is crucial for treating SLE and OP. 29,30 (Mechanism of action of IL-4 in SLE and OP is shown in Figure 10)…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, repairing the dynamic balance between Th1/Th2/Th17/Treg cells is crucial for treating SLE and OP. 29,30 (Mechanism of action of IL-4 in SLE and OP is shown in Figure 10)Figure 9.Mechanism of action between CD4 + Th and Th1/Th2/Th17/Treg cells.Figure 10.Mechanism of action of IL-4 in SLE and OP.…”
Objective This study aimed to explore the relationship between systemic lupus erythematosus (SLE) and osteoporosis (OP) based on bioinformatics. Methods The expression profiles of SLE and OP gene chips were searched through the GEO database, and the differentially expressed genes (DEGs) were screened out to obtain the intersection. Then, the Funrich software was used to predict the upstream miRNAs of the intersection genes, and the miRNA–mRNA relationship network was constructed. Afterward, the String database and Cytoscape software were used to construct the protein interaction network of the intersection genes to screen out the key genes. Finally, the functions and related pathways of key genes were analyzed by using the DAVID database. Results ①A total of 140 intersection genes of SLE and OP were obtained; ②There were 217 miRNAs regulating the intersection genes; ③IL-4, FOS, TLR1, TLR6, CD40LG, CCR1 were the key genes in the protein interaction network; ④The DAVID enrichment analysis mainly covered the positive regulation of cytokine production, the regulation of osteoclast differentiation, macrophage activation and other biological processes, involving Toll-like receptor signaling pathway, T cell receptor signaling pathway, Th1, Th2, and Th17 cells Differentiation, IL-17 signaling pathway. Conclusions SLE and OP still have some highly overlapping differential gene expressions under the background of complex gene networks. The gene functions and signaling pathways involved can simultaneously regulate the two diseases, suggesting that there is a close relationship between the molecular mechanisms of the two diseases, and that it may be a target of drugs that interfere with two diseases at the same time.
“…Therefore, repairing the dynamic balance between Th1/Th2/Th17/Treg cells is crucial for treating SLE and OP. 29,30 (Mechanism of action of IL-4 in SLE and OP is shown in Figure 10)…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, repairing the dynamic balance between Th1/Th2/Th17/Treg cells is crucial for treating SLE and OP. 29,30 (Mechanism of action of IL-4 in SLE and OP is shown in Figure 10)Figure 9.Mechanism of action between CD4 + Th and Th1/Th2/Th17/Treg cells.Figure 10.Mechanism of action of IL-4 in SLE and OP.…”
Objective This study aimed to explore the relationship between systemic lupus erythematosus (SLE) and osteoporosis (OP) based on bioinformatics. Methods The expression profiles of SLE and OP gene chips were searched through the GEO database, and the differentially expressed genes (DEGs) were screened out to obtain the intersection. Then, the Funrich software was used to predict the upstream miRNAs of the intersection genes, and the miRNA–mRNA relationship network was constructed. Afterward, the String database and Cytoscape software were used to construct the protein interaction network of the intersection genes to screen out the key genes. Finally, the functions and related pathways of key genes were analyzed by using the DAVID database. Results ①A total of 140 intersection genes of SLE and OP were obtained; ②There were 217 miRNAs regulating the intersection genes; ③IL-4, FOS, TLR1, TLR6, CD40LG, CCR1 were the key genes in the protein interaction network; ④The DAVID enrichment analysis mainly covered the positive regulation of cytokine production, the regulation of osteoclast differentiation, macrophage activation and other biological processes, involving Toll-like receptor signaling pathway, T cell receptor signaling pathway, Th1, Th2, and Th17 cells Differentiation, IL-17 signaling pathway. Conclusions SLE and OP still have some highly overlapping differential gene expressions under the background of complex gene networks. The gene functions and signaling pathways involved can simultaneously regulate the two diseases, suggesting that there is a close relationship between the molecular mechanisms of the two diseases, and that it may be a target of drugs that interfere with two diseases at the same time.
“…Interestingly, IRF1 is the key factor of PD-L1 promoter function, while PD-L2 is mainly regulated by STAT1/3 [ 33 ], which also explain our results that only PD-L2 is upregulated in LXN −/− macrophages. It has been reported that PD-1 ligands (PD-Ls) contribute to the M2 polarization and immunosuppressive effects of macrophages [ 48 ], and PD-L2 expression correlated with other established markers for alternatively activated macrophages [ 49 ]. As early as ten years ago, Huber et al reported that PD-L2 appears to be a more specific and distinctive marker for M2, and IL-4 induced the expression of PD-L2 on classically activated macrophages, however, LPS increased the expression of PD-L1 on M2 [ 50 ].…”
Latexin (LXN) plays an important role in tumorigenesis and inflammatory response and as a tumor suppressor in many tumors. However, whether LXN regulates tumorigenesis through immune regulation remains uncertain. Here, we demonstrate that LXN deficiency increases hematopoietic stem cells, as well as affects the proportion of immune cells in the peripheral system. Animal studies show that mice loss of LXN promotes tumor growth in subcutaneous tumor model and AOM/DSS-induced colorectal cancer model. We found that loss of LXN promotes macrophage M2 polarization and PD-L2 expression in macrophage, thus, inhibits the function of T cells. Adoptive transfer of wild-type macrophage rescues the function of T cells in LXN-deficient mice. LXN deficiency in hematopoietic lineage exacerbates colorectal carcinogenesis, and targeted inhibition of PD-L2 ameliorates cancer growth in LXN-deficient mice. Mechanistically, we demonstrate that LXN inhibits STAT3 transcriptional activity by targeting inhibition of JAK1 in macrophages. LXN deficiency enhances PD-L2 expression rather than PD-L1 in macrophages, which lead to inhibition of T cells in tumor microenvironment. Collectively, we define a critical role of LXN/JAK1/STAT3 signal in macrophage and highlights the potential role of LXN in tumor immune-escape by regulating macrophage polarization, as well as the expression of immune checkpoint PD-L2.
“…OVA can be used to induce the AR model 20 and was used to treat sorted macrophages from healthy controls for 0, 6, 12, 24, or 48 h at a concentration of 5 mg/ml 21 . In some cases, macrophage M2 polarization was induced by IL‐4 at a concentration of 20 ng/ml 22 …”
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. M2 macrophage polarization can reduce inflammation and repair tissue injury during AR development. Studies have substantiated the involvement of miRNAs in AR pathogenesis. Herein, the molecular mechanism of miR‐214‐3p in AR development was explored. To mimic the AR environment, ovalbumin (OVA) was used to treat macrophages. MiR‐214‐3p and glycogen synthase kinase 3 beta (GSK3B) expression in nasal mucus tissues and macrophages was assessed by RT‐qPCR. The M2 phenotypic signature of CD206 in macrophages was assessed by flow cytometry. The protein expression of GSK3B and M2 macrophage markers (ARG‐1 and IL‐10) was evaluated by western blotting. The correlation between miR‐214‐3p and GSK3B was validated by a luciferase reporter assay. We found that miR‐214‐3p was overexpressed in macrophages and nasal mucus tissues from AR patients. MiR‐214‐3p facilitated M2 polarization of macrophages upon OVA stimulation. Mechanistically, miR‐214‐3p targeted the GSK3B 3′ untranslated region in macrophages. In addition, GSK3B was downregulated in macrophages and nasal mucus tissues from AR patients. In rescue assays, GSK3B downregulation reversed the inhibitory effects of miR‐214‐3p silencing on M2 polarization of macrophages treated with OVA. Overall, miR‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B.
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