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.
Project description:The study aimed to identify proteins associated with rheumatoid arthritis. Dysregulated proteins were linked to inflammation, immune response and oxidative stress.
Project description:Single-cell analysis of the transcriptome, T cell immune receptors, and surface proteome (CITE-seq) from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with pre-existing autoimmune diseases (rheumatoid arthritis n = 5, psoriasis n = 4, or multiple sclerosis n = 3), as well as COVID-19 patients without pre-existing autoimmunity as controls (n = 10) to investigate altered immune responses.
Project description:Periodontitis (PD) is one of the most common human inflammatory diseases, yet the immunological mechanism linking oral and systemic immune responses are not well defined. Here, we show that the accumulation of interleukin-17 (IL-17)-producing γδT (γδT17) cells occurs not only in the oral cavity, but also in the peripheral lymph nodes and spleens in experimental periodontitis in mice. Strikingly, oral γδT17 cells derived from experimental periodontitis migrated to the inflamed joint and led to an exacerbation of rheumatoid arthritis (RA) in a collagen-induced arthritis model in mice. Mechansitically, we demonstrated that the dysbiosis in periodontitis led to an increase in production of complement component 3 (C3)-enriched extracellular vesicles (EVs) derived from macrophages. These C3-enriched EVs were taken up by γδT cells and stimulated intracellular C3a receptor to drive IL-17A production in γδT cells. Our findings revealed an previously unrecognized immunological mechanism linking periodontitis to RA through the accumulation and migration of oral γδT17 cells.
Project description:Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially methylated genes between RA versus healthy using Illumina human methylation arrays in order to identify new epigenetic targets.
Project description:Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially expressed genes between RA at risk or RA versus healthy using RNA sequencing in order to identify new therapeutic targets.
