Objective The immune response arises from a fne balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanismof action of SULF A and addressed the identifcation of its molecular target in human dendritic cells (hDCs).Methods Adjuvant efect and immunological response to SULF A were assessed on DCs derived from human donors. Inaddition to testing various reporter cells, target identifcation and downstream signalling was supported by a reverse pharmacology approach based on antibody blocking and gene silencing, crosstalk with TLR pathways, use of human allogeneicmixed lymphocyte reaction.Results SULF A binds to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2) and initiates an unconventionalmaturation of hDCs leading to enhanced migration activity and up-regulation of MHC and co-stimulatory molecules without release of conventional cytokines. This response involves the SYK-NFAT axis and is compromised by blockade orgene silencing of TREM2. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, andincreased interleukin-10 release after lipopolysaccharide stimulation.Conclusion SULF A is the frst synthetic small molecule that binds to TREM2. The receptor engagement drives diferentiation of an unprecedented DC phenotype (homeDCs) that contributes to immune homeostasis without compromising lymphocyte activation and immunogenic response. This mechanism fully supports the adjuvant and immunoregulatory activityof SULF A. We also propose that the biological p

Summary: ADViSELipidomics is a novel Shiny app for preprocessing, analyzing and visualizing lipidomics data. Ithandles the outputs from LipidSearch and LIQUID for lipid identification and quantification and the data fromthe Metabolomics Workbench. ADViSELipidomics extracts information by parsing lipid species (using LIPID MAPSclassification) and, together with information available on the samples, performs several exploratory and statisticalanalyses. When the experiment includes internal lipid standards, ADViSELipidomics can normalize the data matrix,providing normalized concentration values per lipids and samples. Moreover, it identifies differentially abundantlipids in simple and complex experimental designs, dealing with batch effect correction. Finally, ADViSELipidomicshas a user-friendly graphical user interface and supports an extensive series of interactive graphics.