LAUSR

Background: Plasmacytoid dendritic cells (pDCs) play an important role in linking innate and adaptive immune responses and selectively express Toll-like receptor (TLR) 7 and TLR9 that sense RNA and DNA respectively thus regulating the secretion of type I interferons (IFN) and other inflammatory cytokines such as TNF [1]. pDCs have been directly implicated in psoriasis immunopathology and are activated following anti-viral vaccination, with vaccination also linked to psoriatic arthritis onset [2-3]. Inflammation of the enthesis (enthesitis) is a cardinal spondyloarthritis associated lesion so we hypothesized the presence of enthesis resident pDCs Objectives: To investigate whether the human enthesis contains a resident pDC population and to compare the responses of TLR7/9 agonists on entheseal pDCs function relative to peripheral blood derived pDCs. Methods: Normal interspinous process enthesis and matched peripheral blood (PB) were obtained from patients (n=11) undergoing spinal decompression or scolosis corrective surgery. Cells were isolated from perientheseal bone by mechanical digestion. Cells were stimulated with either TLR7 agonist (imiquimod) or TLR9 agonist (ODN-2216). Flow cytometry was used to phenotype pDCs, and intracellular staining used to measure IFNα and TNF. IFNα from supernatant was also measured by ELISA. Results: pDCs were identified in the human enthesis with a typical phenotype (CD45+HLA-DR+CD123+CD303+CD11c-). By intracellular FACS, following ODN or imiquimod stimulation, IFNα and TNF was detected in entheseal pDCs and also PB. IFNα and TNF induction trended upwards in entheseal pDC when compared with unstimulated pDCs. IFNα was also detected by ELISA following ODN or imiquimod stimulation of entheseal derived pDCs. Conclusion: The human enthesis contains a resident population of pDCs that produce IFNα and TNF following induction with relevant TLR agonists. For the first time, our findings provide a link between viral illness and vaccination and pivotal innate immune cell production of IFNα and TNF. References: [1] Melissa Swiecki and Marco Colonna, The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 2015 Aug;15(8):471-85. [2] Gunes AT, Fetil E, Akarsu S, et al., Possible Triggering Effect of Influenza Vaccination on Psoriasis. J Immunol Res. 2015;2015:258430. [3] Nestle FO, Conrad C, Tun-Kyi A, et al., Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med. 2005 Jul 4;202(1):135-43. Disclosure of Interests: Qiao Zhou: None declared, Richard Cuthbert: None declared, Abdulla Watad: None declared, Tobias Russell Grant/research support from: PhD Project is funded by Novartis., Hannah Rowe: None declared, Almas Khan: None declared, Peter Millner: None declared, Peter Loughenbury: None declared, Abhay S Rao: None declared, Robert Dunsmuir: None declared, Charlie Bridgewood: None declared, Dennis McGonagle Consultant for: Lilly, Novartis UCB, Speakers bureau: Lilly, Novartis UCB