Biology subjects

Gabrielsson, S.

Publications and source records attributed to Gabrielsson, S..

3 recordsLinked to original sources

bioRxiv2026

The metabolic profile of Extracellular Vesicles identifies and separates patients with Sarcoidosis and Anti-Synthetase Syndrome

Sarcoidosis is a multisystem disorder that primarily affects the lungs and is characterizedby granulomatous inflammation. However, much of the underlying disease mechanisms remain poorly understood. Extracellular vesicles (EVs) are small membrane-bound particles released by all cells and carry various cargos including metabolites. They are involved in intercellular communication that can be dysregulated in diseases.This study characterizes the metabolic cargo of EVs isolated from bronchoalveolar lavage fluid (BALF), using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis, in patients with sarcoidosis (n=37), compared to healthy controls (n=10). Additionally, the sarcoidosis signature was compared to another pulmonary disorder, anti-synthetase syndrome (ASyS, n=10). Arachidonic acid (AA) results were verified by ELISA. A total of 1202 metabolites were detected, with 111 annotated ones further analyzed. EVs from sarcoidosis patients showed distinct metabolomic profiles compared to both ASyS patients and healthy controls, with 38 annotated metabolites differentially expressed in any of the groups. In both annotated and non-annotated data, sarcoidosis patients clustered separately from ASyS patients and healthy individuals. Furthermore, sarcoidosis patients clustered in 3 subgroups, whereof one was similar to ASyS patients and one stood out as showing higher cell counts in BALF. Higher AA levels were found in sarcoidosis patient EVs by LC-MS, and AA results were verified by ELISA. Our data show that BALF EV metabolites are disease-dependent and support the notion thatsarcoidosis patients should be further subgrouped for better diagnosis and treatment.

immunology↗

bioRxiv2024

Imaging single particle profiler to study nanoscale bioparticles using conventional confocal microscopy

Single particle profiler is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles and lipoproteins in single particle and high throughput manner. The original version requires the single photon counting modules for data acquisition. Here, we present imaging-based SPP (iSPP) which can be performed by imaging a spot over time in common imaging mode with photomultiplier tubes. We also provide a user-friendly software with graphical user interface to facilitate the application of this technique. We demonstrate that iSPP can be used to decipher lipid-protein interactions, membrane modifications by drugs and the heterogeneity of extracellular vesicles isolated from cells lines and urine of human donors.

biophysics↗

bioRxiv2024

Small Extracellular Vesicle Signaling and Mitochondrial Transfer Reprograms T Helper Cell Function in Human Asthma

Small extracellular vesicles (sEVs) are known to orchestrate cell-cell communication, but the role of sEV signaling via mitochondria in perpetuating asthmatic airway inflammation is unknown. Myeloid-derived regulatory cells (MDRCs) are known to control CD4+ T cell responses in asthma. We demonstrate that airway MDRC-derived sEVs from asthmatics mediate T cell receptor engagement and transfer of mitochondria that induce antigen-specific activation and polarization of Th17 and Th2 cells; these cells are drivers of chronic airway inflammation in asthma. CD4+ T cells internalize sEVs containing mitochondria predominantly by membrane fusion, and blocking mitochondrial oxidant signaling in MDRC-derived sEVs mitigates T cell activation. Reactive oxygen species-mediated signaling that elicits T cell activation in asthmatics is sEV-dependent. Additionally, a Drp1-dependent mechanism in pro-inflammatory MDRCs promotes mitochondrial packaging within sEVs, which then co-localize with the polarized cytoskeleton and mitochondrial networks in recipient T cells. Importantly, intranasal transfer of mitochondria packaged sEVs enhances airway inflammation and Th polarization in vivo in a murine model of asthma. Thus, our studies indicate a previously unrecognized role for mitochondrial fission and sEV-mediated mitochondrial transfer-mediated signaling in dysregulated T cell activation and Th cell polarization in asthma which could constitute a novel therapeutic target.

immunology↗