Biology subjects

Scheffel, J.

Publications and source records attributed to Scheffel, J..

3 recordsLinked to original sources

bioRxiv2025

Preserved suppressive function despite loss of Foxp3: insights into the identity of regulatory T cells

Regulatory T (Treg) cells are essential for maintaining immune homeostasis, with Foxp3 acting as the master transcription factor governing their differentiation and function. The acquisition of effector signatures in Treg cells is closely tied to the surrounding tissue-specific immune environment and typically occurs alongside Foxp3 expression. In this study, we investigated the transcriptomic and functional consequences of Treg-mediated regulation in a Th2-driven disease setting. The application of both in vitro systems and in vivo disease models allowed us to mimic Th2-mediated environments. We could demonstrate Th2-driven loss of Foxp3 expression in Treg cells in vitro and in vivo. Transcriptomic analysis revealed a maintained Treg signature despite the loss of active Foxp3 expression. Functional characterization of Tregs both in vitro and in vivo uncovered a preserved suppressive capacity even in the absence of Foxp3. Our findings unveil that, despite loss of Foxp3, a preserved Treg signature remains intact enabling the regulation of Th2-mediated diseases. The persistence of this regulatory transcriptome highlights the importance for developing Treg-cell therapy strategies in cancer and autoimmune diseases independent of Foxp3 expression.

immunology↗

bioRxiv2021

Label-free imaging of macrophage phenotypes and phagocytic activity in the human dermis in vivo using two-photon excited FLIM

Macrophages (M{Phi}s) are important immune effector cells that promote (M1 M{Phi}s) or inhibit (M2 M{Phi}s) inflammation and are involved in numerous physiological and pathogenic immune responses. Their precise role and relevance, however, is not fully understood because of the lack of non-invasive quantification methods. Here, we show that two-photon excited fluorescence lifetime imaging (TPE-FLIM), a label-free non-invasive method, can visualize M{Phi}s in human dermis in vivo. We demonstrate in vitro that human dermal M{Phi}s exhibit specific TPE-FLIM properties that distinguish them from the main components of the extracellular matrix and other dermal cells. We visualized M{Phi}s, their phenotypes and phagocytosis in the skin of healthy individuals in vivo using TPE-FLIM. Additionally, machine learning identified M1 and M2 M{Phi}s with a sensitivity of 0.88{+/-}0.04 and 0.82{+/-}0.03 and a specificity of 0.89{+/-}0.03 and 0.90{+/-}0.03, respectively. In clinical research, TPE-FLIM can advance the understanding of the role of M{Phi}s in health and disease.

biophysics↗

bioRxiv2018

The human secretome - the proteins secreted from human cells

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving {beta}-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.

molecular biology↗