AB0011 CYTOMETRIC ANALYSIS OF ACTIVATED ENTHESEAL TISSUE RESIDENT T-CELLS REVEALS IL-17F AS THE DOMINANT IL-17 ISOFORM EXPRESSED BY INNATE AND ADAPTIVE LYMPHOCYTES

Background The IL-17/IL-23 pathway has been implicated in many inflammatory diseases such as ankylosing spondylitis, psoriatic arthritis, bowel disease and psoriasis, led to the development of several IL-17 inhibitors. enthesis is connective tissue where tendon or ligament attaches bone. Enthesitis cardinal pathological process spondyloarthritis (SpA) related T-cell derived cytokines including IL-17A, IL-17F TNFα are thought be central SpA immunopathology [1-3] . Clinical advances from inhibition both IL-17A shown great success treating psoriasis. However, our understanding biology at human rudimentary. Objectives Investigate expression identify innate adaptive subsets capable IL-23-independent production IL-17. Methods Peripheral blood spinal samples collected patients undergoing decompression surgery for scoliosis correction. Immune cell populations were isolated, peripheral blood, lymphocyte population was isolated using red lysis mechanical isolation used samples. T-cells stimulated with anti-CD3 (100ng/ml) soluble CD28 72hrs RPMI media. 3-4hrs before end stimulation GolgiPlug added cells harvested analysis intracellular & via flow cytometry fixed frozen further CyTOF analysis. same setup IL-23 stimulations (50ng/ml) without anti-IL-23p19 (20ng/ml) downstream cytokine assessed a multiplex bead immunoassay. Results preferentially expressed over by CD4+ after activation. Only small percentage found express co-express IL-17F. CD8+ lower than their counterpart, again being predominant isoform this type. Analysis types within peri-entheseal bone revealed similar trend PBMC, albeit, observed. rare γδ enthesis. additional enhanced CD4 T-cells; yet alone could not induce production. Addition an IL-23p19 neutralising antibody reduced levels equivalent those seen TCR activation showing that solely dependent on presence IL-23. Conclusion This first study looking IL17F induction normal entheses biological differences between these family members emerged. References [1]Tsukazaki H, Kaito T. Role IL-23/IL-17 Pathway Pathogenesis Spondyloarthritis. Int J Mol Sci 2020;21(17), doi:10.3390/ijms21176401 [2]Mei Y, Pan F, Gao J, et al. Increased serum patient spondylitis. Clin Rheumatol 2011;30(2):269-73, doi:10.1007/s10067-010-1647-4 [3]Ceribelli A, Motta Vecellio M, Trials Supporting Axis Axial Front Immunol 2021;12(622770, doi:10.3389/fimmu.2021.622770 Figure 1. Summary IL17F, IL17A IL17A/F co-expression cytometry. N=3. CD8 measured following (100ng/ml). Error bars representative mean range. Acknowledgements work funded collaboration UCB who provided support access work. Disclosure Interests Nicole McDermott Grant/research from: UCB, Tom Macleod Abhay S Rao: None declared, Vishal Borse: Peter Loughenbury: Robert Dunsmuir: Almas Khan: Ash Maroof Employee of: Dennis McGonagle UCB.