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Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation
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 pre...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148166/ https://www.ncbi.nlm.nih.gov/pubmed/37115585 http://dx.doi.org/10.1084/jem.20220595 |
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author | Zec, Kristina Schonfeldova, Barbora Ai, Zhichao Van Grinsven, Erinke Pirgova, Gabriela Eames, Hayley L. Berthold, Dorothée L. Attar, Moustafa Compeer, Ewoud B. Arnon, Tal I. Udalova, Irina A. |
author_facet | Zec, Kristina Schonfeldova, Barbora Ai, Zhichao Van Grinsven, Erinke Pirgova, Gabriela Eames, Hayley L. Berthold, Dorothée L. Attar, Moustafa Compeer, Ewoud B. Arnon, Tal I. Udalova, Irina A. |
author_sort | Zec, Kristina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10148166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101481662023-04-30 Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation Zec, Kristina Schonfeldova, Barbora Ai, Zhichao Van Grinsven, Erinke Pirgova, Gabriela Eames, Hayley L. Berthold, Dorothée L. Attar, Moustafa Compeer, Ewoud B. Arnon, Tal I. Udalova, Irina A. J Exp Med Brief Definitive Report 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. Rockefeller University Press 2023-04-28 /pmc/articles/PMC10148166/ /pubmed/37115585 http://dx.doi.org/10.1084/jem.20220595 Text en © 2023 Zec et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Definitive Report Zec, Kristina Schonfeldova, Barbora Ai, Zhichao Van Grinsven, Erinke Pirgova, Gabriela Eames, Hayley L. Berthold, Dorothée L. Attar, Moustafa Compeer, Ewoud B. Arnon, Tal I. Udalova, Irina A. Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title_full | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title_fullStr | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title_full_unstemmed | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title_short | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
title_sort | macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148166/ https://www.ncbi.nlm.nih.gov/pubmed/37115585 http://dx.doi.org/10.1084/jem.20220595 |
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