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:Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory diseases that appear to occur in tandem. Autoantibodies against citrullinated peptide antigens linked pathogeneses with PD preceding RA. However, the mutual impact PD exerts on RA and vice versa has not yet been defined. To address this issue, we set up an animal model and analyzed how the prime inducers of citrullination - Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans – differ in their pathogenic potential. Our experimental setup included collagen induced arthritis (CIA) in the mouse, oral inoculation with P. gingivalis or A. actinomycetemcomitans to induce alveolar bone loss and the combination of both diseases in inverted orders of events. Label-free quantitative proteome analysis revealed that P. gingivalis and A. actinomycetemcomitans led to differential expression patterns in the synovial membranes that were reminiscent of cellular and humoral immune responses, respectively. The P. gingivalis and A. actinomycetemcomitans specific signatures in the synovial proteomes suggest a role for oral pathogens in shaping disease subtypes and setting the stage for subsequent therapy response.
2020-12-04 | PXD020397 | Pride
Project description:EMG produced TPA metagenomics assembly of the Oral microbiome Metagenome (human oral metagenome) data set.
| PRJEB25206 | ENA
Project description:EMG produced TPA metagenomics assembly of PRJNA932553 data set (Oral microbiome in periodontitis).
| PRJEB65452 | ENA
Project description:EMG produced TPA metagenomics assembly of PRJNA479723 data set (Nanopore metagenomics).
| PRJEB42552 | ENA
Project description:EMG produced TPA metagenomics assembly of PRJEB54966 data set (Papua New Guinean oral metagenomes).