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Biology subjects

Rauer, M.

Publications and source records attributed to Rauer, M..

4 recordsLinked to original sources

Preimplantation factor (PIF) is an endogenous inhibitor of potassium channel KV1.3 regulating neutrophil function during pregnancy

Pregnancy is a unique period regarding immune cell regulation. Within the placenta, maternal immune cells play a central role in immune surveillance and tissue remodeling. However, regulatory mechanisms of systemic immunity during pregnancy are less clear. Here, we show that neutrophil function is altered in pregnant mice (E13.5), indicated by increased slow rolling velocity and reduced adhesion. Mechanistically, PreImplantation factor (PIF), a 15 amino acid peptide which is produced by human and murine trophoblast cells of the placenta, is continuously secreted into the maternal circulation and plays a key role in modulating neutrophil function via blocking the voltage-gated potassium channel KV1.3. This resulted in impaired intracellular Ca2+ signaling and subsequently disturbance of neutrophil post-arrest modifications and a higher susceptibility to physiological shear forces in vivo and in vitro. Furthermore, PIF-mediated KV1.3 blockade impaired E-selectin-mediated release of S100A8/A9 and phagocytosis. Taken together, we have identified PIF as an important modulator of neutrophil function during pregnancy suggesting a critical role in regulating innate immune responses throughout gestation.

immunology↗

Macrophage renewal in the small intestine governs early-life control of streptococci

Group B Streptococcus (GBS) is both a common intestinal colonizer that is transmitted intergenerationally, and a primary cause of neonatal sepsis worldwide. However, the innate immune mechanisms that restrict the pathogen at the intestinal barrier early in life remain poorly understood. Using an enteral GBS-colonization model in infant mice, we found that lamina-propria (LP) macrophages controlled both GBS-colonization densities and invasion in an age-dependent fashion. LP macrophages turnover and differentiation were strongly impacted by topology. In the small intestine, monocytes infiltration of the LP occurred from birth on in response to perinatally acquired microbiota, whereas in the colon it was driven by the weaning reaction. Moreover, macrophages of the small intestine mounted a robust, MyD88-dependent inflammatory response to GBS, while those of the colon remained largely unaffected. Together, these findings demonstrate that region-specific macrophage dynamics early in life critically influence host-pathogen-interactions during GBS-colonization.

immunology↗

ELAV mediates circular RNA biogenesis in neurons

Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally (>75%) depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In brain tissue, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.

molecular biology↗

snakePipes enable flexible, scalable and integrative epigenomic analysis

The scale and diversity of epigenomics data has been rapidly increasing and ever more studies now present analyses of data from multiple epigenomic techniques. Performing such integrative analysis is time-consuming, especially for exploratory research, since there are currently no pipelines available that allow fast processing of datasets from multiple epigenomic assays while also allow for flexibility in running or upgrading the workflows. Here we present a solution to this problem: snakePipes, which can process and perform downstream analysis of data from all common epigenomic techniques (ChIP-seq, RNA-seq, Bisulfite-seq, ATAC-seq, Hi-C and single-cell RNA-seq) in a single package. We demonstrate how snakePipes can simplify integrative analysis by reproducing and extending the results from a recently published large-scale epigenomics study with a few simple commands. snakePipes are available under an open-source license at https://github.com/maxplanck-ie/snakepipes.

genomics↗