NDORMS DPhil & MSc by Research
Targetting Th17 immune responses in Spondyloarthritis
OUTLINE OF RESEARCH PROPOSAL
In Spondyloarthritides, a group of chronic inflammatory conditions that affect up to 1-2% of the popu-lation, a major pathogenetic role is mediated by Th17 cells. Th17 are a subset of effector T cells, that mediate inflammation and tissue damage of joints and enthesis in Ankylosing Spondylitis and Psoriatic Arthritis. New biological drugs against the signature cytokine of this subset, IL-17, are currently under development, but the exact role of Th17 in the context of the immune response and of the local tissue inflammation is still unclear.
The pro-inflammatory effect of Th17 is controlled through processes that involve regulatory T cells, or Tregs. Since Th17 and inducible Tregs originate from the same precursor and share several develop-mental requirements, it is thought that their differentiation is reciprocally inter-connected. Both meta-bolic signals or the nutritional state can influence the cell fate. Moreover mature Th17 are plastic and can transdifferentiate to regulatory phenotype under specific conditions, such as via molecular path-ways involved in environmental sensing like the aryl hydrocarbon receptor (AhR).
The research will explore the effect of environmental and metabolic cues on the reciprocal generation of pathogenic Th17, that drive autoimmunity and inflammation, and Tregs, that immune responses.
Our long term aim is to obtain information on the plasticity of T cell responses in human inflammatory arthritis and to exploit it to develop possible novel therapies.
This project will provide excellent training in a molecular and biochemical techniques including flow cytometry, ELISA and culture with ex vivo stimulation of cells including isolated immune subsets.