Deciphering the immunoregulatory network governing antigen presenting myeloid cells

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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.