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Biology subjects

Supper, V.

Publications and source records attributed to Supper, V..

3 recordsLinked to original sources

Vgamma9+Vdelta2+Tcell-mediated purging of Listeria monocytogenes-infected epithelial cells requires butyrophilin 3A genes

Intracellular bacteria produce antigens, which serve as potent activators of {gamma}{delta} T cells. Phosphoantigens are presented via a complex of Butyrophilins (BTN) to signal infection to human V{gamma}9+V{delta}2+ T cells. Here, we established an in vitro system allowing for studies of V{gamma}9+V{delta}2+ T cell activity in coculture with epithelial cells infected with the intracellular bacterial pathogen Listeria monocytogenes. We report that the V{gamma}9+V{delta}2+ T cells efficiently purge such cultures from infected cells. This effector function requires the expression of members of the BTN3A family on epithelial cells. Specifically, the BTN3A1 and BTN3A3 are redundant in their ability to present antigen to V{gamma}9+V{delta}2+ T cells. Since BTN3A1 is the only BTN3A associated with phosphoantigen presentation our study suggests that BTN3A3 may present different classes of antigens to mediate V{gamma}9+V{delta}2+ T cell effector function against L. monocytogenes-infected epithelia.

immunology↗

Genetic dependencies associated with transcription factor activities in human cancer cell lines

Transcription factors (TFs) are key components of the aberrant transcriptional programs in cancer cells. In this study, we used TF activity (TFa), inferred from the downstream regulons as a potential biomarker to identify associated genetic vulnerabilities in cancer cells. Our linear model framework, integrating TFa and genome-wide CRISPR knockout datasets identified 1,770 candidate TFa-target pairs across different cancer types and assessed their survival impact in patient data. As a proof of concept, through inhibitor screens and genetic depletion assays in cell lines, we validated the dependency of cell lines on predicted targets linked to TEAD1, the most prominent TF from our analysis. Overall, these candidate pairs represent an attractive resource for early-stage targets and drug discovery programs in oncology.

bioinformatics↗

Attenuated foreign body response to subcutaneous implant in regenerative spiny mice (Acomys)

Spiny mice (Acomys) can regenerate after injury with minimal fibrosis. Whether Acomys retains the fibrosis-free feature in response to implanted devices is unknown, so we implanted polydimethylsiloxane (PDMS) subcutaneously in Acomys and Mus, a non-regenerative counterpart. In Acomys, we found reduced myeloid cell infiltration, fibroblast activation, and collagen deposition around the PDMS implant. These results suggest that Acomys can regulate FBR and may hold the key to improving implant lifetime and functionality.

bioengineering↗