Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation

• DOI: 10.1084/jem.20220595
• Publication Date: 2023-04-28T14:37:19Z
• Authors: Kristina Zec; Barbora Schonfeldova; Zhichao Ai; Erinke Van Grinsven; Gabriela Pirgova; Hayley L. Eames; Dorothée L. Berthold; Moustafa Attar; Ewoud B. Compeer; Tal I. Arnon; Irina A. Udalova
• Keywords: Inflammation; Neutrophil Infiltration; Arthritis; Macrophages; Synovial Membrane; Brief Definitive Report; Humans; Antigens; 3. Good health

The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, quantitative way present evidence synovial begins with the activation of lining macrophages. We show lining, but not sublining macrophages phagocytose immune complexes containing model antigen. Using antigen-induced arthritis (AIA) model, demonstrate on recognition antigen–antibody complexes, undergo significant activation, which is dependent interferon regulatory factor 5 (IRF5), produce chemokines, most notably CXCL1. Consequently, at onset inflammation, neutrophils are preferentially recruited vicinity antigen-laden niche. As progresses, disperse across whole synovium form swarms resolution. Our study alters paradigm as immunosuppressive important instigators inflammation.