Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the ability of portovenously administered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT-1l) rats received Brown Norway (BN, RT-1n) rat donor splenocytes, via either the portal vein (PV group) or the peripheral vein (IV group). The immune responses of LEW rats, treated with either donor BN or third party Wistar King A (WKA, RT-1k) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). The effect of intravenous gadolinium chloride (GDCl3) on the blockade of Kupffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppression was blocked by pretreatment with GDCl3. The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCl3 decreased the percentage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a signal of the CTLA4-B7 pathway played an important part in inhibiting the interaction of CD28 and its B7 ligands.
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PMID:Donor dendritic cells and recipient Kupffer cells in the induction of donor-specific immune hyporesponsiveness. 1139 45

Background: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) that has a poor 5-year overall survival rate due to its lack of precise therapeutic targets. Identifying potential prognostic markers of AITL may provide information regarding the development of precision medicine. Methods: RNA sequence data from PTCL and patient clinic traits were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify DEGs between the different PTCL subtypes and investigate the relationship underlying co-expression modules and clinic traits. Gene ontology (GO) and protein-protein interaction (PPI) network analyses based on DAVID and the STRING website, respectively, were utilized to deeply excavate hub genes. Results: After removing the outliers from the GSE65823, GSE58445, GSE19069, and GSE6338 datasets using the results from an unsupervised cluster heatmap, 50 AITL samples and 55 anaplastic large cell lymphoma (ALCL) samples were screened. A total of 677 upregulated DEGs and 237 downregulated DEGs were identified in AITL and used to construct a PPI network complex. Using WGCNA, 12 identified co-expression modules were constructed from the 5468 genes with the top 10% of variance, and 192 genes from the Turquoise and Brown modules were with a Gene Significance (GS) cut-off threshold >0.6. Eleven hub genes (CDH1, LAT, LPAR1, CXCL13, CD27, ICAM2, CD3E, CCL19, CTLA-4, CXCR5, and C3) were identified. Only CTLA-4 overexpressed was found to be a poor prognostic factor according to survival analysis. Gene set enrichment analysis (GSEA) identified and validated the intersection of key pathways (T cell receptor, primary immunodeficiency, and chemokine signaling pathways). Conclusion: Our findings provide the framework for the identification of AITL co-expression gene modules and identify key pathways and driving genes that may be novel treatment targets and helpful for the development of a prognostic evaluation index.
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PMID:Identification of hub genes and key pathways associated with angioimmunoblastic T-cell lymphoma using weighted gene co-expression network analysis. 3123 75