Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 27, 2025

Abstract Background The small intestine harbors a rich array of intestinal intraepithelial lymphocytes (IELs) that interact with structural cells to collectively sustain gut immune homeostasis. Dysregulation homeostasis was implicated in the pathogenesis multiple autoimmune diseases, however, whether this is disrupted lupus background remains unclear. Methods We performed single-cell RNA sequencing (scRNA-seq) analyses elucidate and milieu epithelium MRL/Lpr mice (Lpr mice) MRL/Mpj control (Mpj mice). Comprehensive including unsupervised clustering, trajectories, cellular communication were performed. primary findings from scRNA-seq further validated by quantitative polymerase chain reaction (qPCR), flow cytometry, vivo experiments selenium supplementation. Results observed significant reduction CD8αα + IELs, accompanied marked increase CD8αβ IELs Lpr mice. Additionally, subsets CD8 exhibiting significantly enhanced effector functions found be markedly enriched Intercellular patterns within epithelial specifically altered Moreover, revealed decreased TCRγδ T (γδT) associated reduced aryl-hydrocarbon receptor repressor ( AHRR ) expression subsequent oxidative stress ferroptosis Antioxidant effectively reversed loss γδT mice, improved barrier, alleviated symptoms. Conclusions Our high-resolution atlas enhances understanding provides new insights into mediated dysregulation.

Language: Английский

A distribution-guided Mapper algorithm

BMC Bioinformatics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 5, 2025

The Mapper algorithm is an essential tool for exploring the data shape in topological analysis. With a dataset as input, outputs graph representing features of whole dataset. This often regarded approximation Reeb classic uses fixed interval lengths and overlapping ratios, which might fail to reveal subtle dataset, especially when underlying structure complex. In this work, we introduce distribution-guided named D-Mapper, utilizes property probability model intrinsic characteristics generate density-guided covers provide enhanced features. Moreover, metric accounting both quality overlap clustering extended persistent homology measure performance Mapper-type algorithms. Our numerical experiments indicate that D-Mapper outperforms various scenarios. We also apply SARS-COV-2 coronavirus RNA sequence explore different virus variants. results can vertical horizontal evolutionary processes viruses. code available at https://github.com/ShufeiGe/D-Mapper . from based on model. work demonstrates power fusing probabilistic models with

Language: Английский

Immunology of multiple sclerosis: an update

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: 38(3), P. 180 - 187

Published: April 30, 2025

Purpose of review The immunological processes that lead to multiple sclerosis (MS) and occur during the progressive phase disease are manifold still not well understood. This summarizes new insights on this topic were gained through recent studies with diverse scientific approaches. Recent findings While genetic risk clearly contributes MS, external factors play a key role in its pathogenesis as well. Epstein-Barr virus infection correlates significantly MS seems be major causal factor. Even though our knowledge human gut microbiome connection central nervous system is far from being complete, several have proven gut–brain axis influences neuroinflammation progression MS. It has become much clearer solely T cell-mediated but also strongly driven by B cells pathogenic antibodies. Beyond peripheral immune cells, glial their interactions neurons important players contributing activity Summary Taken together, publications context implicate multitude noncanonical mechanisms need further explored regarding interplay contribution degenerative course disease.

Language: Английский