Adoptive Transfer Murine Model of Granulomatous Experimental Autoimmune Thyroiditis

Experimental autoimmune thyroiditis (EAT) is a chronic inflammatory autoimmune disease that can be induced in genetically susceptible animals by immunization with mouse thyroglobulin (MTg) in an appropriate adjuvant or by the adoptive transfer of MTg-sensitized donor spleen cells, activated in vitro with MTg, into naive recipients. In the adoptive transfer model used in our laboratory, donor cells activated with MTg alone induce a relatively mild chronic lymphocytic form of EAT (L-EAT), in which the thyroid infiltrate consists primarily of mononuclear cells, and the thyroid inflammation persists for several months. When the same donor cells are activated with MTg together with anti-IL-2R and/or IL-12, a more severe and histologically distinct granulomatous form of EAT is induced in recipient mice. In addition to having distinct histopathologic features, granulomatous EAT (G-EAT) differs from L-EAT in that granulomatous thyroid lesions are not chronic. After reaching maximal severity 21 days after cell transfer, G-EAT thyroid lesions either resolve or the thyroids become atrophic and fibrotic by day 35. In this review, the histopathologic features of G-EAT and L-EAT are described, and our studies with the adoptive transfer G-EAT model which have focused on the mechanisms involved in induction of G-EAT in mice, and the evolution of G-EAT lesions to resolution of inflammation or fibrosis, are reviewed.     

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

Toll‐like receptor (TLR) 4 signalling is critical for innate immunoinflammatory response and widely triggers the development of various types of clinical diseases. MicroRNA‐7 (miR‐7) is well documented to play an important regulatory role in various biological events. However, the exact role of miR‐7 in TLR4 signalling pathway remains to be fully elucidated. In the present study, we found that miR‐7 expression in TLR4 signalling‐activated bone marrow‐derived macrophages (BMDMs) stimulated by LPS was dramatically increased. Importantly, miR‐7 deficiency significantly enhanced the production of related inflammatory cytokines including IL‐1β, IL‐6 and IL‐12, as well as TNF‐α, on LPS‐activated BMDMs, accompanied by elevated transduction of TLR4 signalling including Myd88‐dependent and Myd88‐independent pathways, whereas miR‐7 overexpression significantly decreased the transduction of TLR4 signalling and the production of related inflammatory cytokines. Mechanistically, we identified family with sequence similarity 177, member A (FAM177A) as a novel target molecule of miR‐7. Furthermore, down‐regulation of FAM177A using RNAi could impair the transduction of TLR4 signalling. Finally, down‐regulation of FAM177A also reversed the effect of miR‐7 deficiency on TLR4 signalling transduction and production of related inflammatory cytokines on BMDMs. Therefore, we provide the new evidence that miR‐7 acts as a novel negative fine‐tuner in regulating TLR4 signalling pathways by targeting FAM177A, which might throw light on the basal understanding on the regulatory mechanism of TLR4 signalling and benefit the development of therapeutic strategies against related clinical diseases.     

唐氏综合征胎儿全基因组miRNA表达谱特征及其染色体分布

目的研究唐氏综合征(DS)胎儿全基因组miRNA表达谱及其编码基因的染色体分布特征。方法采用Illumina深度测序技术对6例DS胎儿(DS组)和6例正常胎儿脐带血(对照组)单个核细胞小RNA测序比对分析,确定DS全基因组miRNA表达谱及其编码基因的染色体分布特征。结果两组共检测到395种miRNA,编码于316个miRNA基因。其中149种miRNA在两组中的表达具有显著性差异(DS组中6种上调,143种下调),有51种miRNA特异性表达于对照组。21号染色体编码的14个miRNA基因在DS组中有1个(miR-802)高表达,4个(let-7c、miR-99a、miR-125b和miR-155)低表达,余下9个在两组样本中均未表达。两组样本miRNA基因表达的染色体分布趋于一致,但miRNA基因表达丰度的分布却不尽相同:DS组主要分布于8、16、17和21号染色体,对照组主要分布于3、8、14、16、17和22号染色体。结论 DS胎儿脐带血单个核细胞具有其特定的miRNA表达谱和染色体分布特征,表达丰度差异分布的染色体编码miRNA可能在DS各临床性状的形成过程中具有重要作用。     

微小RNA介导的牙周炎与动脉粥样硬化相关机制的研究进展

牙周炎是一种主要由菌斑生物膜所引起的牙周支持组织慢性炎症破坏性疾病,与宿主的免疫反应相关。牙周致病菌可通过一过性菌血症进入血液循环系统,引发血管炎症反应,增加心血管疾病患病风险。微小RNA(microRNA)作为近年来小分子RNA的研究热点,可在表观遗传学水平调控基因表达,参与炎症调节。本文综述了牙周致病菌通过microRNA调控免疫炎症反应的机制,从而介导动脉粥样硬化的发生、发展,为牙周炎与动脉粥样硬化疾病关联的分子机制研究提供新的思路。此外,通过探索动脉粥样硬化与牙周炎相关特异性microRNA的表达模式,可为未来诊断或治疗心血管疾病提供新的参考。     

Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn’s Disease: A Systematic Review

1. Download : Download high-res image (161KB)
2. Download : Download full-size image