Abstract
Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types and are present in bodily fluids, such as blood, urine, and bile. EVs are thought to play a key role in intracellular communication. Based on their size and density, EVs are classified into small, medium, or large EVs. Cargo composition in EVs reflects physiological changes in health and disease. Patients with irritable bowel syndrome (IBS) exhibit visceral hypersensitivity and mood disorders. Stressful episodes often precede disease symptoms in IBS patients. Stress-induced symptoms include, but are not limited to, abdominal pain and mood swings. Perceived stress responses are mediated by two known G protein-coupled receptors (GPCRs), corticotropin-releasing factor receptor 1 and 2 (CRFRs). CRFRs belong to the Class B secretin receptor family of GPCRs. Here, we show that CRFRs were present in human and murine plasma, and in EVs purified from mouse serum. CRFRs were present in plasma from IBS patients and healthy controls. EVs secreted from immune cells influence both adaptive and innate immune responses via exchange of EVs between different immune cell types. B7-2 (CD86), a plasma membrane antigen-presenting protein, is present on EVs secreted from dendritic, B-, and mast cells, whereas CD9 is present on EVs secreted from dendritic and intestinal epithelial cells. We found that plasma CRFR levels positively correlated with B7-2+ EVs (R = 0.8597, p < 0.0001), but no association was seen with CD9+ EVs. Plasma CRFRs expression negatively correlated with IBS severity scores. Our data suggests that plasma EVs from immune cells carry CRFRs as cargos and influence cell-cell communication in health and disease.
Highlights
Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types
We first determined that CRFRs were present in human plasma from healthy individuals and patients with irritable bowel syndrome (IBS)-D
Immunoblot of diluted (1:100) serum samples revealed the presence of multiple CRFR bands; six distinct band sizes for were observed (Figure 1a)
Summary
Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types. Based on their biogenesis, size, or densities, EVs are classified into different categories [1]. EVs formed from the membranes of intracellular compartments via the endocytic pathways are referred to as exosomes. Exosomes range from 50–100 nm in diameter with buoyant densities of. Microvesicles that originate from the outward blebbing of the plasma membrane are often referred to as ectosomes or microparticles and range from 100–1000 nm in diameter. The recent guidelines posted by the International Society for Extracellular Vesicles recommends referring to EVs
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