(588f) Identification and Characterization of a First Responder Cells: A Dendritic Cell Subtype That Coordinates Adaptive Immune Responses

While it is known that dendritic cells (DCs) are a crucial cell for antigen presentation and initiation of adaptive immunity, DCs are a highly heterogeneous population of cells. It is currently unknown if all cells participate equally in antigen presentation and immune activation. Recent reports have indicated there is a subpopulation of DCs that exhibits highly increased cytokine secretion to toll-like receptor (TLR) signaling but to date these cells have been difficult to isolate and characterize. Using fluorescently labeled polystyrene microparticles (MPs) conjugated with various TLR agonist molecules, we isolated this subtype of cells we call First Responders (FRs). FRs exhibit similar increases in cytokine (TNFα) secretion seen in prior literature and statistically significant increases in MP uptake. FRs also coordinate neighboring innate immune cell activation via paracrine signaling. Furthermore, when adoptively transferred into mice with a model antigen OVA, FRs were both necessary and sufficient to trigger adaptive immune responses, both antibody and CD8 t cells. FRs express CD11c and MHCII, typical markers of DCs, but also express CD11b and SIRPα, typical of cDC2 cells. To understand the phenotype even further, we performed both bulk and single cell mRNA sequencing on FRs and observed increases distinct expression profile with increases in several immune and metabolic genes. After validating the gene expression via flow cytometry, we identified several surface markers unregulated in FRs. The results indicate that FRs have expression of some B cell surface markers, such as CD20 and CD267, but lack CD19 or B220 and also overexpress DC markers such as FTL-3 and CD301b. Due to their importance in innate immune coordination and their crucial role in adaptive immune responses, these cells not only warrant further study but also present an attractive target for vaccine research.