免疫炎性疾病新认识及中西医结合临床对策于清宏沈阳摘要.pptVIP

白芍总苷（total glucosides of paeonia，TGP） OVA免疫 明确现象---TGP抑制免疫应答 抑制T细胞活化增殖 抑制机体对于新入侵抗原的免疫应答 探讨关键表型--TGP抑制DC成熟 被动转移实验：mDC恢复小鼠对于OVA反应 证实TGP抑制DC成熟而导致免疫应答降低 探讨机理--TGP抑制TLR-MyD88/NF-kB活化 ** MyD88 与疾病治疗-RA-CIA模型 CII+CFA CII+IFA 细胞亚群、细胞因子、信号转导 n=10/组 3次重复 16分评分 DBA1 明确现象-TGP延缓和减轻CIA发病与炎症 提前使用TGP，延缓并减轻CIA发病 机理-TGP抑制DC成熟 降低CII免疫应答 明确表型-TGP降低Th1/Th17细胞亚群和功能 临床验证-TGP降低RA患者Th1/Th17 TNFa产生细胞减少 PSA? TGP? TGP作用后PSA样小鼠体内M1细胞活性降低 TGP – 抑制M1，上调M2（体外） ERAP1 associated with HLA-B27+ve AS Nature Genetics 2011;43:761-767 Picture courtesy of Dr. Eric Reits ERAP1/ERAP2 process antigenic peptide epitopes before loading onto HLA-B27 Nucleus NK/Mo DC Immunoreceptor Recognition of Aberrant B27 CD8+ Arthritogenic Peptides and Autoreactive T Cells ER BiP UPR B27 Misfolding,ER Stress, and UPR Activation No defining mechanism by which HLA-B27 causes AS Altered APC Function CD4+ ERAP2 SNP N392K affects both enzyme activity and specificity The kcat of the enzyme changes by 25-fold Effects on trimming rate are substrate-specific! Vanhille et al. Molecular Genetics Genomic Medicine 2013; 1(2): 98–107 Evnouchidou et al. J Immunol 2012; 189(5):2383 ERAP1 SNPs at positions 528 and 730 affect both enzyme activity and antigen presentation kcat/KM Ki MHCI levels Evnouchidou et al. J Immunol 2011 Length selection can be altered by polymorphic variation Garcia et al. MCP, 2012 Affects activity Affects Specificity Evnouchidou et al. J Immunol 2012; 189(5):2383 SNPs are “scattered” all over the protein structure AS易感基因的贡献值 肠道菌微生态与免疫炎性疾病 AS CD HC Bacteroides Acintobacteria Firmicutes Fusobacteria Proteobacteria AS gut microbiome is different to CD and HC AS CD HC Bacterial control 机械压力的骨赘形成的作用 Ann Rheum Dis 2013 遗传和环境因素共同导致疾病的发生 Nature Med 2012;18:1018 IL23介导的T细胞参与了AS的致病 ？ ？ ？ ？ ？ 强直性脊柱炎的致病机理假说 IL-17 IL-