Project description:The microbiome in Dermatomyositis associated with Interstitial lung disease and rheumatoid arthritis associated with Interstitial lung disease
Project description:Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA), a model that recapitulates features of RA-associated interstitial lung disease (RA-ILD). As patients with RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize lung infiltrating monocytes/macrophages in a mouse model of RA-ILD and determine whether reducing these cells mitigates the development of lung disease. Autoimmune-prone DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for up to 5 weeks and CIA induction. Experimental groups included Sham (saline injection/saline inhalation), CIA (CIA/saline), LPS (saline/LPS), and CIA+LPS (CIA/LPS). Lung disease was assessed by longitudinal imaging, lung function measurements, bronchoalveolar lavage fluid, lung tissues, and lung histopathology. Cell subpopulations were analyzed by single cell RNA-sequencing. Unsupervised clustering revealed 16 discrete clusters among the experimental groups with 2 robust clusters characterized as infiltrating inflammatory monocytes/macrophages for both CIA+LPS and CIA. The interaction of inhalation-induced airway inflammation and autoimmune arthritis results in lung disease associated with uniquely activated infiltrating inflammatory monocytes-macrophages that mediate adverse lung consequences. Whereas the induced monocyte/Mɸ immunophenotype is more aligned to CIA than endotoxin exposure, co-exposure modeling renders unique features that potentially inform the pathogenesis and treatment of RA-ILD.
Project description:microRNA profiling by array of peripheral blood mononuclear cells from patients with early onset psoriatic arthritis, rheumatoid arthritis and healthy controls.
Project description:Autoimmune diseases, such as rheumatoid arthritis, are associated with significant gut microbiota dysbiosis. Here we show that remodelling of 24h rhythms within the gut during inflammatory joint disease drives profound changes in the microbiome and gut permeability.
2023-03-15 | GSE184233 | GEO
Project description:Microbiome in Rheumatoid arthritis