OP0028 CD206+CD163+ PATHOGENIC MACROPHAGES ENRICHED IN RHEUMATOID ARTHRITIS SYNOVIAL TISSUE WITH DISTINCT TRANSCRIPTIONAL SIGNATURES

Background: Synovial tissue macrophages are an exquisitely plastic pool of innate cells that play a key role in RA disease progression. However, the precise nature, diversity, and function of macrophage subsets within the inflamed joint remains unexplored. Objectives: Therefore, the aims of this study are to phenotypically, transcriptionally and functionally characterise synovial tissue macrophages residing within the inflamed joint. Methods: Rheumatoid Arthritis, Psoriatic Arthritis, Osteoarthritis and healthy control synovial-tissue biopsies and synovial-fluid mononuclear cells were analysed using the following panel (CD40,-CD45,-CD64,-CD68,-CD163,-CD206,-CD253,-CCR4,-CCR7,-CXCR1,-CXCR3). CD206+CD163+ and CD206-CD163- macrophages were sorted from RA synovial-tissue by FACSAria sorter; RNAseq and FLIM analysis, autologous T-cell co-culture and heathy fibroblast experiments performed. Cytokine expression was measured by MSD immunoassay. Results: RA synovial tissue and fluid macrophages display markers typical of both M1 (CD40+CD253+) and M2 (CD206+CD163+) macrophages with a spectrum of macrophage activation states identified. Within this spectrum, significant enrichment of dominant CD206+CD163+ macrophage-subtype is present in synovial tissue versus fluid (p Conclusion: This data identifies for the first-time enrichment of a previously undescribed dysfunctional dominant and transcriptionally distinct macrophage subtype in RA synovial tissue. Taken together, this data provides a greater understanding of the critical role tissue-resident macrophages play in perpetuating inflammation in RA. Further investigation of the molecular patterns and cues that shape specific synovial macrophage subsets may provide opportunities to reinstate RA joint homeostasis. Disclosure of Interests: Megan Hanlon: None declared, Mary Canavan: None declared, Qingxuan Song Employee of: Janssen Research & Development, Nuno Neto: None declared, Phil Gallagher: None declared, Ronan Mullan: None declared, Conor Hurson: None declared, Michael Monaghan: None declared, Sunil Nagpal Employee of: Janssen Research & Development, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Consultant of: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB