Biology subjects

Totzeck, M.

Publications and source records attributed to Totzeck, M..

3 recordsLinked to original sources

bioRxiv2026

Reg3β removes aged neutrophils after myocardial infarction

AO_SCPLOWBSTRACTC_SCPLOWRecruitment and resolution of immune cell accumulation after myocardial infarction (MI) is critical for effective wound healing and prevention of maladaptive remodeling. Numerous signals are known to recruit neutrophils, critical drivers of inflammation, but knowledge about signals containing and resolving their accumulation is limited. We discovered that Regenerating-islet derived protein 3 beta (REG3{beta}) limits the persistence of neutrophils after MI, thereby promoting resolution of inflammation. REG3{beta} selectively binds to aged and hyperactive neutrophils and induces rapid cell death, enabling clearance via macrophage-mediated efferocytosis. Selective binding of REG3{beta} is achieved by interaction with paucimannosylated proteins that translocate from azurophile granules to the plasma membrane in an activation- and age-dependent manner. Endocytotic uptake and accumulation of REG3{beta} in lysosomes initiates programmed cell death of neutrophils via lyosomal membrane permeabilization and release of cathepsins. Our work establishes REG3{beta} as a local immune checkpoint essential for neutrophil resolution and cardiac repair.

immunology↗

bioRxiv2022

Peyers Patch B cells undergo cell death via neutrophil-released toxic DNA following sterile tissue injury

Lymphocyte contraction (LC) in central immune organs is a concomitant of sterile tissue injury, for example after stroke. Intestinal Peyers patches (PP) harbor large numbers of B cells, but how sterile tissue injury leads to LC in PP has not been explored. We observed rapid and macroscopically evident shrinkage of PP after stroke and myocardial infarction. Light-sheet fluorescence microscopy and flow cytometry revealed a strong reduction in the number of PP-resident B cells. Mechanistically, tissue injury triggered the activation of neutrophils that released B cell-toxic neutrophil extracellular traps (NETs) decorated with citrullinated histone-H3. Antibody-mediated or genetically induced neutrophil-loss, NETs-degradation or blockade of their generation completely reversed B cell loss and preserved the tissue architecture of PP. We also found NET-like elements in human post-stroke plasma. Hence, we propose that targeting NET-generation or -function counteracts post-injury B cell contraction in PP and thereby maintains immune homeostasis at mucosal barriers. In briefHigh numbers of B cells reside in the intestinal Peyers patches. Tuz et al. revealed that in response to sterile tissue injury, activated neutrophils release histone-decorated DNA into the circulation which induces B cell death. The loss of B cells results in the shrinkage of Peyers patches and reduced amounts of secretory IgA. HighlightsO_LIStroke and myocardial infarction induce the melting of Peyers patch C_LIO_LILight-sheet microscopy and cytometry revealed B cell loss in Peyers patch C_LIO_LIPost-injury activated neutrophils release NETs and trigger B cell death C_LIO_LIInhibition of NETs rescues B cell loss and degeneration of Peyers patch C_LI

immunology↗

bioRxiv2022

Rapid and fully automated blood vasculature analysis in 3D light-sheet image volumes of different organs

Blood vasculature represents a complex network of vessels with varying lengths and diameters that are precisely organized in space to allow proper tissue function. Light-sheet fluorescence microscopy (LSFM) is very useful to generate tomograms of tissue vasculature with high spatial accuracy. Yet, quantitative LSFM analysis is still cumbersome and available methods are restricted to single organs and advanced computing hardware. Here, we introduce VesselExpress, an automated software that reliably analyzes six characteristic vascular network parameters including vessel diameter in LSFM data on average computing hardware. VesselExpress is ~100 times faster than other existing vessel analysis tools, requires no user interaction, integrates batch processing, and parallelization. Employing an innovative dual Frangi filter approach we show that obesity induces a large-scale modulation of brain vasculature in mice and that seven other major organs differ strongly in their 3D vascular makeup. Hence, VesselExpress transforms LSFM from an observational to an analytical working tool.

bioinformatics↗