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Mercado Hansson posted an update 1 year, 7 months ago
In this review article, we focus on results derived from basic studies that have attempted to elucidate the immune modulatory mechanisms of liver constituent cells and clinical trials that induced immune tolerance after liver transplantation by utilizing the immune-privilege potential of the liver.We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway in vitro and in vivo. Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new niche targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.In a syngeneic murine melanoma (MEL) model, we recently reported an in situ vaccination response to combined radiation (RT) and intra-tumoral (IT) injection of anti-GD2 hu14. 18-IL2 immunocytokine (IC). This combined treatment resulted in 71% complete and durable regression of 5-week tumors, a tumor-specific memory T cell response, and augmented response to systemic anti-CTLA-4 antibody checkpoint blockade. While the ability of radiation to diversify anti-tumor T cell response has been reported, we hypothesize that mice rendered disease-free (DF) by a RT-based ISV might also exhibit a heightened B cell response. C57BL/6 mice were engrafted with 2 × 106 GD2+ B78 MEL and treated at a target tumor size of ~200 mm3 with 12 Gy RT, IT-IC on day (D)6-D10, and anti-CTLA-4 on D3, 6, and 9. Serum was collected via facial vein before tumor injection, before treatment, during treatment, after becoming DF, and following rejection of subcutaneous 2 × 106 B78 MEL re-challenge on D90. Flow cytometry demonstrated the presencehumoral memory response. This endogenous tumor-specific antibody response does not appear to have therapeutic efficacy but may serve as a biomarker for an anti-tumor T cell response.Background The unique immunomodulatory capacity of helminth parasites has been investigated as a novel strategy in the prevention of allograft rejection after transplantation. This review was conducted to fully evaluate the specific effects of helminth therapy on allograft survival reported in published studies of animal models of allogeneic transplantation. Method Following PRISMA protocol guidelines, a literature search was conducted using PubMed, MEDLINE via OvidSP, along with additional manual searches of selected reference lists. Publications describing helminth intervention within allograft transplantation models were screened for relevance to eligibility criteria. Primary and secondary outcomes were extracted using standardized data collection tables. The SYRCLE risk of bias assessment tool was used for quality assessment. CHR-2845 inhibitor Due to heterogeneity of study designs, meta-analysis could not be performed; rather outcomes are presented as a narrative synthesis with concept mapping. This review was registered ir a specific allograft, to elucidate the optimal dose and route of administration, and to better understand the modulation of immune responses that can mediate tolerance.Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets has been reported in SSc; however, there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients (n = 20) and healthy controls (n = 10) were analyzed by mass cytometry using a 36-marker (cell surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and mucosal associated invariant T (MAIT) cells in patients, accompanied by increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall, this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation-mediated “functional adaptation” of immune cells.In nature, plant viruses are mostly transmitted by hemipteran insects, such as aphids, leafhoppers, and whiteflies. However, the molecular mechanisms underlying the interactions between virus and insect vector are poorly known. Here, we investigate the proteomic interactions between tomato yellow leaf curl virus (TYLCV, genus Begomovirus, family Geminiviridae), a plant virus, and its vector whitefly (Bemisia tabaci) species complex. First, using a yeast two-hybrid system, we identified 15 candidate whitefly proteins interacting with the coat protein of TYLCV. GO and KEGG pathway analysis implicated that these 15 whitefly proteins are of different biological functions/processes mainly including metabolic process, cell motility, signal transduction, and response to stimulus. We then found that the whitefly protein tumorous imaginal discs (Tid), one of the 15 whitefly proteins identified, had a stable interaction with TYLCV CP in vitro, and the DnaJ_C domain of Tid301-499aa may be the viral binding site. During viral retention, the expression of whitefly protein Tid was observed to increase at the protein level, and feeding whiteflies with dsRNA or antibody against Tid resulted in a higher quantity of TYLCV in the whitefly body, suggesting the role of Tid in antiviral infection.

