Biology subjects

Niss, K.

Publications and source records attributed to Niss, K..

5 recordsLinked to original sources

bioRxiv2026

Semaglutide Attenuates Neuroinflammation in Mice

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1 RA effects on neuroinflammation remain poorly understood. Here, using a mouse model of lipopolysaccharide-induced neuroinflammation, we investigated how semaglutide coordinates cellular responses to resolve neuroinflammation. We find that semaglutide prevents brain infiltration of neutrophils, excessive cytokine release, and suppresses neuroinflammation-associated transcriptional signatures specifically in microglia, endothelial cells, and a subset of pericytes. Mechanistically, we identify a subset of Glp1r-expressing neurons in the dorsal vagal complex that, upon semaglutide treatment, regulate genes involved in anti-inflammatory signaling. Semaglutide-modulated pathways overlap with inflammatory signatures found in human neurodegenerative diseases, including Alzheimers disease, suggesting broad relevance for conditions involving neuroinflammation. Together, these findings reveal how GLP-1R signaling orchestrates resolution of neuroinflammation through coordinated multi-cellular programs.

neuroscience↗

bioRxiv2021

The small and large intestine contain transcriptionally related mesenchymal stromal cell subsets that derive from embryonic Gli1+ mesothelial cells

Intestinal fibroblasts (FB) play essential roles in intestinal homeostasis. Here we show that the small and large intestinal lamina propria (LP) contain similar FB subsets that locate in specific anatomical niches and express distinct arrays of epithelial support genes. However, there were tissue specific differences in the transcriptional profile of intestinal FB subsets in the two sites. All adult intestinal LP mesenchymal stromal cells (MSC), including FB, smooth muscle cells (SMC) and pericytes derive from Gli1-expressing embryonic precursors which we identify as mesothelial cells. Trajectory analysis suggested that adult SMC and FB derive from distinct embryonic intermediates, and that adult FB subsets develop in a linear trajectory from CD81+ FB. Finally, we show that colonic subepithelial PDGFRhi FB comprise several functionally and anatomically distinct populations that originate from an Fgfr2-expressing FB intermediate. Collectively our results provide novel insights into MSC diversity, location, function and ontogeny, with implications for our understanding of intestinal development, homeostasis and disease.

developmental biology↗

bioRxiv2020

Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages

Type I interferons (IFNs) play an essential role in antiviral immunity, correlate with severity of systemic autoimmune disease, and are likely to represent a key component of mRNA vaccine-adjuvanticity. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood due to pleiotropic effects in multiple cell types. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-{gamma} induces T-bet expression and IgG2c isotype switching prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c+ GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1 + GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through parallel Th1 and Tfh cell-dependent pathways.

immunology↗

bioRxiv2018

Bow-tie motifs enable protein multifunctionality by connecting cellular processes in the interactome

Abstract (172/175 words)Cell type-specific protein interactomes are promising resources for the understanding of cell functionality and genetic perturbations in cellular states. However, while many low-and top-level aspects of interactome topology have been mapped, we still lack an understanding of the topological motifs at the intermediate level, where connectivity between cellular processes takes place. We combine conventional dendritic cell lineage 1 (cDC1)-specific expression data with a high-quality protein interactome, subsequently creating an information-rich cDC1-specifc interactome matrix that displays topological information on an unprecedented 36.7 million protein pairs at once. By dissecting the interactome-matrix, we reveal that the bow-tie motif is a major connector of cellular processes and an extremely widespread topology in the protein interactome. In aggregation, the bow-tie motifs form a scaffold within the interactome that hierarchically link cellular processes together. We further demonstrate that the bow-tie motifs design can enable protein multifunction. Our generic approach allows a topological characterization and visualization of any large network, facilitating a more effective usage of community-produced interaction data, and is applicable to any cell types interactome.

systems biology↗

bioRxiv2018

Glycolytic repression and reduced GLP-1 secretion by active Farnesoid X Receptor in enteroendocrine L cells achieved via PKLR

Rise in intestinal glucose increases GLP-1 secretion by enteroendocrine L cells. GLP-1, in turn, stimulates insulin secretion. Farnesoid X Receptor (FXR) represses this pathway by manipulating the L cell glycolysis, thus reducing insulin- and GLP-1 secretion. The mechanism by which FXR manipulates the L cell glycolysis is unclear. In this study, we construct an L cell specific protein-protein interactome and identify all significantly active protein complexes, inferred by co-expression scores, in FXR-activated and control L cells. Contrary to previous reports, we find extensive glycolytic enzyme activity in FXR-activated L cells. We present how FXRs repression of the glycolytic enzyme, pyruvate kinase (PKLR), is causing the reduction in glycolytic activity. This mechanistic insight may aid development of drugs targeting the GLP-1 pathway.

systems biology↗