Immunomodulation of pathogenic B-cell responses by gut-derived metabolites in Juvenile Idiopathic Arthritis
Concept
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.
Facts and Figures
Dr. E C Rosser
UCL Division of Medicine, University College London
e.rosser@ucl.ac.uk
Meet the Team
Versus Arthritis YPFS
Scottish Network for Arthritis in Children
JIA-at-NRAS
Juvenile Arthritis Research
Objectives
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.
Goals/Milestones
Milestones before project start date (1st of Feb 2023):
- Recruit research assistant.
- Complete recruitment for JIA patients and controls.
Milestones during 36-month project timeline:
- Measure candidate metabolites in JIA and perform B-cell immunophenotyping on matched blood samples.
- Assess potential of different diets to alter B cell function and severity of experimental arthritis.
- Prepare grant applications for further funding and to grow research group.
Patient Voice
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.