Accumulating evidence demonstrates that pathogenic changes at the gut-site, such as dysbiosis of the gut-microbiota, drives inflammation in the synovium of patients with autoimmune arthritis. However, the exact nature of the gut-derived signals that condition the pro-arthritogenic potential of inflammatory cells are yet to be clarified. Here, using juvenile idiopathic arthritis (JIA) as a model, I will investigate whether, and how, specific metabolites, whose production is controlled by the gut-microbiota and/or diet, impact B-cell pathogenicity in JIA. The findings from this proposal will generate new insights into the mechanisms controlling the gut-joint axis in childhood arthritides.
This proposal will test the hypothesis that the availability of gut-derived metabolites drives B-cell pathogenicity in autoimmune arthritis via two research objectives:
Objective 1: Identify gut-derived metabolites that are associated with altered B-cell phenotype in JIA.
Objective 2: Ascertain the mechanisms by which candidate metabolites modulate pro-arthritogenic B-cell function in vivo.
Milestones before project start date (1st of Feb 2023):
Milestones during 36-month project timeline:
Patient research partners have been extensively consulted during the design and drafting of this project to make it relevant to patients/families, make sure it is understandable, as well as on the research methods and patient facing documents (see non-technical summary for detailed information). Patient partners will be consulted at all the major milestones, and throughout the project to ensure maximal dissemination to the wider JIA community.