Biology subjects

Bein, J.

Publications and source records attributed to Bein, J..

3 recordsLinked to original sources

bioRxiv2026

Stroke-induced lipocalin-2-expressing red pulp macrophages reprogram peripheral immunity

Acute ischemic stroke (AIS) induces profound systemic immune alterations that contribute to infection susceptibility. Here, we identify lipocalin-2 (LCN-2) as a rapidly induced and conserved regulator of stroke-associated immunosuppression. Using 3-MACE-Seq, cytokine profiling, and immunofluorescence in C57BL/6J mice subjected to transient middle cerebral artery occlusion (tMCAO), we show that LCN-2 is strongly upregulated in splenic red pulp macrophages (RPMs) within 24 hours and again 7 days post-tMCAO. LCN-2-expressing RPMs form immunological synapses with CD3+ T cells, thereby impacting T cell trafficking. Recombinant LCN-2 directly reprogrammed T cells and monocytes toward hyporesponsive, tolerogenic phenotypes by suppressing inflammatory cytokines, impairing chemotaxis, enhancing phagocytosis, and uncoupling oxidative burst. Human spleens likewise displayed LCN-2-expressing CD68+ RPMs, and LCN-2 preconditioning of monocytes reproduced reduced HLA-DR, CD80, CD206, and ROS with increased uptake of E. coli bioparticles. These findings identify LCN-2 signaling as a central orchestrator of stroke-induced peripheral immunoreprogramming and a potential therapeutic target to mitigate post-stroke immunodepression. SummaryAcute ischemic stroke induces LCN-2 in splenic red pulp macrophages, which reprogram T cells and monocytes toward tolerogenic, hyporesponsive states. Mouse and human data identify LCN-2 as a driver of peripheral immunodepression and a potential target to reduce infection risk. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/733904v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@fb0caforg.highwire.dtl.DTLVardef@1fdcd41org.highwire.dtl.DTLVardef@1ae99b0org.highwire.dtl.DTLVardef@1ec0837_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

immunology↗

bioRxiv2026

ProxiCapture Reveals Context-Dependent CRBN Interactore Landscape of Molecular Glue Degraders

Molecular glue degraders represent a rapidly expanding class of small molecules that reprogram E3 ubiquitin ligases to ubiquitinate and degrade disease-relevant proteins. Despite their therapeutic potential, the rational design of molecular glues remains challenging, underscoring the need for unbiased discovery strategies to identify new chemical targets. To address this challenge, we developed ProxiCapture, an affinity-based proteomics workflow that models the systemic behavior of molecular glues by combining purified CRBN-{Delta}HBD protein with native cell or tissue lysates. Systematic application of ProxiCapture across eight cancer cell lines, three maturation states of immune cells, and paired primary healthy and tumor tissues, revealed a comprehensive atlas of pomalidomide interactors, including previously uncharacterized targets. These findings reveal that degrader-dependent interactors of CRBN are context-dependent, requiring broad, physiologically and systemically anchored sampling to uncover the full "glueable" proteome. Taken together, this study establishes a scalable platform that accelerates molecular glue discovery by capturing cell- and tissue-specific recruitment profiles and predicting system-wide degrader effects.

cancer biology↗

bioRxiv2025

Exosomal cargo genes as biomarkers and potential mediators of exosome-driven cell communication in Pleural Mesothelioma

Pleural mesothelioma (PM) is a rare yet aggressive and heterogeneous cancer type with very poor survival rates. Due to its long latency period and nonspecific symptoms, the disease is usually detected at advanced stages, limiting available treatment options and leading to poor survival rates. So far, the disease can only be confirmed through invasive thoracoscopic biopsy. Moreover, the proposed circulating protein biomarkers lack sensitivity and specificity, highlighting the urgent need for novel approaches. In our previous work, we characterized the transcriptomic profile of extracellular vesicles secreted by PM cells and demonstrated their feasibility as a source of circulating biomarkers. To further investigate the role of circulating RNA in tumor progression and its potential use in non-invasive testing for PM, here we present a detailed characterization of RNA cargo carried by PM exosomes - a distinct subset of extracellular vesicles known to serve as key mediators of intercellular communication. By utilizing primary cell cultures established from tissue samples of 11 PM and 6 non-PM patients, followed by exosome isolation, and total RNA sequencing of RNA from isolated exosomes, matching cells, and tissues, we provide new evidence on exosomal RNA secretion, regulation of PM-exosome cargo genes, and their potential functions in recipient cells. We show that PM-exosomal cargo is enriched in genes associated with proliferation, whose key transcriptional factors are SETDB1, FOXM1 and GATA2. We identified Pcbp2, Srsf1 and Srsf9, RNA-binding proteins, which may be involved in selective cargo sorting into PM-exosomes. Our analysis identified six secreted genes, including GAS5, AL031666.3, RSLD1D1, AC103740.2, ADAM10, and AC020892.1, whose exosomal expression was associated with patient survival, as promising biomarkers for patient diagnosis, stratification, and prognosis assessment. Finally, we identify potential target genes of candidate LncRNAs biomarkers and processes in which they are involved.

cancer biology↗