Investigation of Conventional T cells from spinal enthesis tissue including pharmacological antagonism

Ankylosing Spondylitis (AS) is a seronegative chronic immune-mediated inflammatory arthritis which is part of the spondyloarthropathy (SpA) family of chronic joint diseases. AS mainly affects the spine and sacroiliac joints with enthesitis (inflammation at points where tendon, ligament, and joint capsules are inserted into bone) representing a key pathological lesion, furthermore, in severe AS cases this can culminate in complete fusion of the spine. It is believed that the pro-inflammatory cytokines including tumour necrosis factor α (TNF α and Interleukin-17A (IL-17A) drive the inflammation at the enthesis, however currently there is limited data on which cells at the enthesis are producing IL-17A. Recent studies have shown that normal human spinal entheses harbour several innate immune cell populations including type 3 innate lymphoid cells (ILC3s), myeloid cells and also γδ T-cells. However, a description of adaptive immune T-cells at the enthesis has not been reported.
This project investigated whether spinal enthesis including peri-entheseal bone harboured resident CD4+ and CD8+ T-cells. Additionally, it evaluates the effects of blocking the production of pivotal SpA-related cytokines, TNFα and IL-17A in an “in vitro enthesitis model”. Also, it investigates T cell plasticity via gene expression of T helper IL-17 producing cells and regulatory T cells (Th17 and Treg respectively) markers following in vitro induction of entheseal inflammation.