Deciphering the immunoregulatory network governing antigen presenting myeloid cells

摘要 父奖励R35GM145290的这一管理补充的目标是购买流 用于高通量自动样本采集和分析的细胞分析仪系统。这些设备将 允许测量各种研究的免疫细胞亚群中的多种属性。读出指数 包括评估细胞群体频率、增殖能力、血统承诺差异 和分化，改变分子信号活性和功能结果的变化 病原体挑战，以及其他衡量标准。简而言之，树突状细胞(DC)负责引导T细胞 细胞反应和巨噬细胞对调节组织炎症很重要。这些免疫力的一个标志 细胞是它们在基因表达谱中固有的可塑性，以控制免疫和耐受。然而，很多 关于共同管理造血的复杂分子网络仍不清楚， 炎症和抗原呈递。不完全的理解是描述他们的 在健康和疾病方面的潜在作用，这也阻碍了成功地开发有效的 免疫疗法。这项拟议研究的长期目标是确定免疫调节的关键作用 稳定期与疾病相比，蛋白质控制DC和巨噬细胞分化和免疫反应 设置。购买带有通用加载器的流式细胞仪将使实验室能够进行 高通量自动样本采集，以评估样本中的多个指数，使用96和 384井板。我们在研究中获得的知识，主要读数仪器是流式细胞仪 分析，将填补我们对DC和巨噬细胞生物学理解的关键空白，并提供重要的见解 进入管理免疫力和耐受性的分子网络。

SUMMARY The goal of this administrative supplement for the parent award R35GM145290 is to purchase a flow cytometric analyzer system for high-throughput automated sample acquisition and analysis. The equipment will allow measurement of multiple properties within various investigated immune cell subsets. Readout indices include assessment of cell population frequencies, proliferation capacities, variances in lineage commitment and differentiation, altered molecular signaling activities and changes in functional outcomes in response to pathogen challenges, among other measurements. Briefly, dendritic cells (DC) are responsible for directing T cell responses and macrophages important for modulating tissue inflammation. A hallmark of these immune cells is their inherent plasticity in gene expression profiles to govern immunity vs. tolerance. However, much remains unknown regarding the complex molecular networks that collectively govern hematopoiesis, inflammation and antigen presentation. Incomplete understanding presents major obstacles to delineating their underlying roles in health and disease, which has also hindered success in developing effective immunotherapies. The long-term goal of the proposed research is to determine how pivotal immunoregulatory proteins govern DC and macrophage differentiation and immune responses in steady-state vs. disease settings. Acquisition of a flow cytometric analyzer with a universal loader will allow the laboratory to engage in high-throughput automated sample acquisition to assess multiple indices within samples employing 96- and 384-well plates. Knowledge gained in our studies, with the chief readout instrument being flow cytometric analysis, will fill key gaps in our understanding of DC and macrophage biology and provide important insights into the molecular networks governing immunity and tolerance.