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

Autor:	Zec K; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Schonfeldova B; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Ai Z; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Van Grinsven E; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Pirgova G; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Eames HL; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Berthold DL; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Attar M; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Compeer EB; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Arnon TI; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK., Udalova IA; Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2023 Aug 07; Vol. 220 (8). Date of Electronic Publication: 2023 Apr 28.
DOI:	10.1084/jem.20220595
Abstrakt:	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, and quantitative way to present evidence that synovial inflammation begins with the activation of lining macrophages. We show that lining, but not sublining macrophages phagocytose immune complexes containing the model antigen. Using the antigen-induced arthritis (AIA) model, we demonstrate that on recognition of antigen-antibody complexes, lining macrophages undergo significant activation, which is dependent on interferon regulatory factor 5 (IRF5), and produce chemokines, most notably CXCL1. Consequently, at the onset of inflammation, neutrophils are preferentially recruited in the vicinity of antigen-laden macrophages in the synovial lining niche. As inflammation progresses, neutrophils disperse across the whole synovium and form swarms in synovial sublining during resolution. Our study alters the paradigm of lining macrophages as immunosuppressive cells to important instigators of synovial inflammation. (© 2023 Zec et al.)
Databáze:	MEDLINE
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