The Danger Model 2: how tissues control Immunity

危险模型 2：组织如何控制免疫力

• 批准号: 8745319
• 负责人: POLLY C MATZINGER
• 金额: $ 34.84万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745319
• 关键词: Adult; Area; Autoimmunity; Bacteria; Budgets; Cell Line; Cells; Collaborations; Communication; Dendritic Cells; Development; Education; Epithelial Cells; Escherichia coli; Genes; Germ-Free; Healed; Health; Immune; Immune response; Immune system; Immunity; Immunologist; Intestines; Modeling; Mus; National Institute of Allergy and Infectious Disease; Natural regeneration; Neonatal; Parasitology; Porphyromonas gingivalis; Reaction; Research; Scientist; Small Interfering RNA; System; T-Lymphocyte; Testing; Thymus Gland; Time; Tissues; Up-Regulation; Vaccines; cancer transplantation; commensal microbes; fighting; healing; infancy; jejunum; neonate; pathogen; response; transcription factor

Because our lab was shut down by the NIAID administration at the end of march this year, we focused on two projects that had some possibility of completion. We did not manage to finish either project, but will continue them through collaborations with other scientists on and off campus. 1) analysis of the stimulatory effect of P gingivalis (PG) on dendritic cells: we compared the stimulatory capacity of PG with that of E coli, and found that PG are almost entirely non-stimulatory. For example, it takes 1000 times more PG LPS than E coli LPS to stimulate dendritic cells. Further, PG has the capacity to degrade several key immune cyctokines made by dendritic cells and/or T cells. 2) analysis of the effect of GATA4: GATA 4 is a transcription factor highly expressed by the epithelial cells of the jejunum. In mice carrying a targeted deletion in jejunal GATA4, the jejunal epithelial cells upregulate a network of immune genes. To determine whether the immune upregulation is a direct effect of the loss of GATA4, or an indirect effect because of GATA4-induced changes in the intestinal flora, we took two approaches. First we generated germ-free GATA4KO mice. Second we used siRNA to downregulate GATA4 in the intestinal cell line, MODE-K. The germ free mice are now sitting, waiting for a collaborator to collect their tissues, as we are not being allowed to spend our budget to do this. The cell line revealed that at least three immune genes are upregulated, in the absence of bacteria, when GATA4 is downregulated by siRNA.

由于我们的实验室在今年3月底被NIAID政府关闭，因此我们专注于两个有可能完成的项目。 我们没有设法完成任何一个项目，而是通过与校园内外的其他科学家的合作来继续他们。 1）分析P牙龈（Pg）对树突状细胞的刺激作用：我们比较了PG的刺激能力与E大肠杆菌的刺激能力，发现PG几乎完全不是刺激性的。 例如，刺激树突状细胞的PG LPS比E Coli LPS的1000倍。 此外，PG具有降解由树突状细胞和/或T细胞产生的几种关键免疫细胞因子。 2）分析GATA4：GATA 4的作用是由空肠上皮细胞高度表达的转录因子。 在空肠GATA4中携带靶标缺失的小鼠中，空肠上皮细胞上调了免疫基因网络。 为了确定免疫上调是GATA4损失的直接影响，还是由于GATA4诱导的肠道菌群变化而产生的间接作用，我们采取了两种方法。 首先，我们生成了无菌的GATA4KO小鼠。 其次，我们使用siRNA在肠细胞系中下调GATA4模式为K。 现在，没有细菌的老鼠正在坐着，等待合作者收集他们的组织，因为我们不允许我们花预算来做到这一点。 细胞系显示，当GATA4被siRNA下调时，在没有细菌的情况下，至少三个免疫基因被上调。