AB0115 CD14+ MYELOID CELLS EXPRESS THE PDC MARKERS BDCA-2, BDCA-4, CD123 UPON DIFFERENTIATION IN BOTH HEALTHY INDIVIDUALS AND SLE PATIENTS

Background Plasmacytoid dendritic cells (pDCs) are crucial mediators of the immune system linking innate and adaptive responses [1]. pDCs exhibit high expression IL-3 receptor (CD123) as well other receptors such BDCA-2 (CD303) BDCA-4 (CD304). These molecules used to identify in mechanistic studies for therapeutic targeting. A recent clinical trial showed a reduction interferon-stimulated gene improvement skin joint inflammation lupus patients who received treatment targeting [2,3]. However, extensive functional single-cell transcriptomic data have previously shown that immunologically inert, not contributing type I IFN production seen with systemic erythematosus (SLE) [4,5]. Objectives To investigate whether markers BDCA-2, BDCA-4, CD123 expressed by myeloid than pDCs. Methods Peripheral blood mononuclear (PBMCs) were obtained from healthy individuals SLE. PBMCs analysed fresh or after 24-hour vitro culture using flow cytometry pDC markers. CD14 + monocytes purified freshly isolated negative selection. For M1 differentiation, cultured 6 days presence GM-CSF; IFN-γ LPS added on day incubated additional 24 hours. M2 M-CSF; IL-4 IL-13 an After 7-day culture, collected, stained cytometry, CytExpert (Beckman Coulter) software. Results On PBMCs, was unique controls. also subset CD3 - CD19 CD11c HLA-DR cells. In some SLE patients, presented positive although at lower level compared (CD3 ). both strong CD123. purification differentiation either (CD14 CD16 CD206 CD80 CD163 low ) phenotype, these seen. macrophages almost universal contrast, meagre but Conclusion We show -previously thought be exclusively pDCs- differentiated controls findings can limit significance those tissue samples simple immunohistochemistry. Finally, been primary contributor interferon signature blood, may explain how related impact disease activity patients. References [1]Psarras A, et al. Nat Rev Rheumatol. 2022 Oct;18(10):575-590. [2]Werth VP, N Engl J Med. Jul 28;387(4):321-331. [3]Psarras, A. & Vital, E.M. Anti-BDCA2 Antibody Cutaneous Lupus Erythematosus. Med 387, 1528-1529 (2022). [4]Psarras, Comm 11, 6149 (2020). [5]Billi, A.C. Sci Transl 14, eabn2263 Acknowledgements: NIL. Disclosure Interests Antonios Psarras: None declared, Zoe Wigston: Edward Vital Speakers bureau: AstraZeneca, Novartis, Paid instructor for: Consultant of: UCB, Pfiser, Aurinia, Lilly, Roche, Genentech, Otsuka, GSK, Capella.