OP0286 Genotypic effects of ankylosing spondylitis associated il7r polymorphisms are mediated through monocytes in inflammation

Background Interleukin 7 (IL-7) plays a key role in T cell survival and proliferation. Both cell-surface expressed and soluble forms of the IL-7 receptor (sIL7R) are recognised. sIL7R has been shown to prolong IL-7 activity in inflammation(. 1 IL7R polymorphisms are associated with multiple inflammatory diseases including ankylosing spondylitis(AS). Higher levels of circulating sIL7R are present in those carrying the risk variant but the cellular sources of soluble IL7R are unclear. Expression quantitative trait loci (eQTL) studies have shown genetically regulated IL7R gene upregulation in monocytes after innate immune stimuli(. 2 Objectives This study aims to characterise the genotypic effects of IL7R polymorphism on monocyte protein surface expression and sIL7R release. Methods Monocyte cell surface IL7R expression was measured by flow cytometry in the presence or absence of LPS or TNF in a cohort of volunteers recruited from the Oxford biobank. Soluble IL7R was quantified by ELISA in purified monocyte cultures stimulated with LPS. RNA sequencing was performed for 8 paired samples of control and recombinant IL-7 exposed stimulated monocytes. Results Surface IL7R expression was induced after 24 hours of LPS stimulation both in isolated monocytes (n=84, p= ex-vivo staining of monocytes from inflamed synovial fluid of SpA showed significant upregulation of IL7R compared to paired PBMC monocytes (n=4, p= Conclusions Monocytes upregulate IL7R expression and soluble IL7R secretion after LPS treatment in a functional, genotype- and TNFalpha-dependant manner. SpA synovial monocytes express IL7R suggesting preactivation. These data draw attention to an unappreciated key myeloid role for AS risk variants at IL7R. References [1] Lundstrom W, et al. PNAS 2013. [2] Fairfax BP, et al. Science 2014. Acknowledgements BPF and PB contributed equally to this work Disclosure of Interest None declared